Patent Publication Number: US-2019185852-A1

Title: Therapeutically modulating apob and apoai

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application claims priority to U.S. Provisional Application No. 62/332,442, entitled “THERAPEUTICALLY MODULATING APOB AND APOAI,” filed May 5, 2016, the disclosure of which is hereby incorporated by reference in its entirety. 
    
    
     GOVERNMENT LICENSE RIGHTS 
     This invention was made with government support under grant numbers 2R56DK046900-17A1 and 5R01DK46900-15 from the National Institutes of Health. The government has certain rights in the invention. 
    
    
     FIELD 
     The subject technology generally relates to methods of altering the expression of proteins involved in lipid transport and metabolism, for example, to prevent and treat cardiovascular diseases and risk factors such as atherosclerosis and hyperlipidemia. 
     INCORPORATION BY REFERENCE 
     All publications, patents, and patent applications cited herein are incorporated by reference in their entirety. U.S. application Ser. No. 14/370,846, filed Jan. 9, 2013, also relates to methods of treating atherosclerosis and hyperlipidemia with a microRNA, the content of which is hereby incorporated by reference in its entirety. 
     BACKGROUND 
     High plasma concentrations of plasma low density lipoprotein (LDL) and low plasma concentrations of high density lipoprotein (HDL) cholesterol levels are risk factors for cardiovascular diseases. Thus, an ideal treatment goal is to simultaneously decrease LDL and increase HDL. 
     SUMMARY OF THE INVENTIONS 
     The subject technology provides methods of administering a microRNA (miR) comprising SEQ ID NO:1, wherein the miR simultaneously reduces plasma LDL, increases plasma HDL, and enhances hepatic fatty acid oxidation (FAO) and reverse cholesterol transport. In some embodiments, the methods of the subject technology reduce hepatic very low density lipoprotein (VLDL) production. 
     In some embodiments of the subject technology, the miR further comprises a sequence with at least 70%, 75%, 80%, 85%, 90% or 95% identity to SEQ ID NO:2. In another embodiment, the miR is hsa-miR-1200 (Dharmacon) (referred to herein as “miR-1200”), and has the sequence of SEQ ID NO:2. See Table 1. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Seed and Full Sequences of miR-1200 
               
            
           
           
               
               
               
            
               
                 MiR 
                 Seed Sequence 
                 Full Sequence 
               
               
                   
               
               
                 Hsa-miR-1200 
                 SEQ ID NO: 1: 
                 SEQ ID NO: 2: 
               
               
                 (″miR-1200″) 
                 UCCUGA 
                 CUCCUGAGCCAUUCUGAGCCUC 
               
               
                   
               
            
           
         
       
     
     In some aspects of the subject technology, a miR comprising SEQ ID NO:1 is administered to a mammal. In some embodiments, the mammal is a mouse. In yet another embodiment, the mammal is an Apoe −/−  mouse. In some embodiments, the mammal is a human. In yet another embodiment, the methods of the subject technology provide for the administration of a therapeutically effective amount of a miR comprising SEQ ID NO:1 to a human in need thereof, wherein the treatment prevents or reduces hyperlipidemia or atherosclerosis. 
     In some embodiments of the subject technology, a therapeutically effective amount of miR comprising SEQ ID NO:1 for treatment of a human is 0.1-2 mg/kg/week. In some of these embodiments, the therapeutically effective amount is 0.1-0.5 mg/kg/week, 0.5-1 mg/kg/week, 1-1.5 mg/kg/week, 1.5-2 mg/kg/week, 0.1 mg/kg/week, 1 mg/kg/week, 1.5 mg/kg/week or 2 mg/kg/week. A person of ordinary skill in the art would understand that this initial dose can be adjusted based on the severity and type of condition being treated, the mode of administration and the response of the individual patient. The dose may also be administered twice a week as a divided dose, biweekly, or as an extended release formulation. 
     In some embodiments of the subject technology, apoAI expression is increased by contacting a cell with an inhibitor of BCL11B. In one aspect of the subject technology, a miR comprising SEQ ID NO:1 increases apoAI transcription by reducing the expression and/or activity of its repressor, BCL11B. In another aspect of the subject technology, a miR comprising SEQ ID NO:1 reduces apoB expression by targeting the 3′-untranslated region of mRNA and enhancing posttranscriptional degradation. In yet another aspect of the subject technology, a miR comprising SEQ ID NO:1 increases hepatic fatty acid oxidation by repressing NCOR1. 
     In some embodiments of the subject technology, apoAI expression is increased by contacting a cell with an inhibitor of NRIP1. The inhibitor may be a nucleic acid inhibitor, such as an siRNA, or it may be a small molecule, peptide or protein inhibitor, such as an antibody or a fusion protein. Inhibitors of NRIP1 may be administered in combination with another inhibitor, such as an inhibitor of BCL11B or apoB expression. In one aspect of the subject technology, an NRIP1 inhibitor is administered to an animal or human in an amount sufficient to increase apoAI expression, thereby causing a therapeutically desirable effect, such as preventing or treating atherosclerosis and/or hyperlipidemia. 
     In some of the methods of the subject technology, a miR comprising SEQ ID NO:1 is administered to prevent, mitigate or reduce atherosclerosis, hyperlipidemia, dyslipidemia, cardiovascular disease. In other methods of the subject technology, a miR comprising SEQ ID NO:1 is administered to prevent, mitigate or reduce insulin resistance, type II diabetes, schizophrenia, fatty liver disease, inflammation, hepatitis C, familial hypercholesterolemia, multiple sclerosis and rheumatoid arthritis. 
     The subject technology provides methods of reducing plasma LDL and increasing plasma HDL without causing liver injury. In one aspect provided herein, miR-1200 significantly reduced plasma LDL- and increased HDL-cholesterol in diet-induced hyperlipidemic mice. In another embodiment, an miR comprising SEQ ID NO:1 reduces plasma LDL and increases plasma HDL in a hyperlipidemic human. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIGS. 1A-1D  show the identification of miRs regulating apoB and apoAI secretion in Huh-7 cells. (A) Huh-7 cells were reverse transfected in duplicate plates with a human miRDIAN mimic 16.0 library (Dharmacon) of 1237 miRs. After 24 hours, cells received complete media with 10% FBS. After another 24 hours, cells were incubated with complete media containing 10% fetal bovine serum (FBS) and oleic acid/BSA complexes (0.4 mM/1.5%) for 2 hours to avoid identification of miRs that affect posttranslational degradation of apoB. Media apoB and apoAI were quantified by ELISA. As a control, different wells in each plate were transfected with Scr (negative) or miR-30c (positive, reduces apoB). (B) Percent change in media apoB and apoAI in two plates exposed to the same miRs compared to Scr control were plotted. (C) The number of miRs that changed media apoB and apoAI to different extents in the second screening were tabulated. (D) Different miR family members with the same seed sequence showed similar effects on media apoB and apoAI. 
         FIGS. 2A-2J  show regulation of apoB secretion by miR-1200 in human hepatoma cells. (A) Reverse transfection of miR-1200 [50 nM] in Huh-7 cells significantly increased miR-1200 levels after 48 h. (B, C) Dose-dependent effects of miR-1200 and anti-1200 on media (B) and cellular (C) apoB. (D, E) Temporal changes in media (D) and cellular (E) apoB levels after treatment with 50 nM of miR-1200, anti-1200 or Scr control. (F) The effect of miR-1200 and anti-1200 on apoB mRNA levels normalized to Scr. (G) Time dependent disappearance of apoB mRNA in cells transfected with miR-1200 and treated with actinomycin D (1 μg/mL). The apoB/18S rRNA ratio at time 0 was set to 100%. (H) Top: Predicted interactions between miR-1200 and apoB mRNA from miRanda. Bottom: The seed interacting site was mutated as indicated, using the primers shown in Table 3 (I) Cells were first transfected with psiCHECK luciferase constructs (1.5 μg/well) containing normal (WT) or mutated (Mut) apoB 3′-UTR sequences. Equal numbers of these cells were transferred to another plate and reverse transfected with either Scr or miR-1200 [50 nM]. The ratios of firefly and Renilla luciferase activities determined after 48 h are shown relative to Scr. (J) Proposed working model: miR-1200 targets the 3′-UTR of apoB, induces mRNA degradation, and decreases the production of apoB-containing lipoproteins. Data are represented as mean±SD. p&lt;0.05, ** P&lt;0.01 and *** P&lt;0.001. 
         FIGS. 3A-3J  show that MiR-1200 increases apoAI secretion by reducing expression of BCL11B, a repressor. (A) Dose-dependent effect of miR-1200 and anti-1200 on apoAI in Huh-7 cells measured after 48 h. (B) Time-dependent changes in media apoAI levels in Huh-7 cells transfected with 50 nM miR-1200, anti-1200 or Scr control. (C) Effect of miR-1200 and anti-1200 on mRNA levels of apoAI normalized to Scr. (D) Temporal changes in apoAI mRNA levels in cells transfected with Scr or miR-1200 and treated with actinomycin D (1 μg/mL). (E) Luciferase activity in Huh-7 cells transfected first with a vector in which human apoAI promoter was cloned upstream of Gaussia luciferase cDNA and then transfected with either miR-1200 or Scr. The luciferase activities were determined after 48 h. Data are presented relative to Scr. (F) MiR-1200 or different siRNAs [50 nM] were reverse transfected in Huh-7 cells. apoAI (left) and apoB (right) were measured in the media after 48 h. (G) Huh-7 cells were co-transfected with different miRs and siRNAs [50 nM]. Secreted apoAI and apoB levels were measured after 48 h. (H) BCL11B mRNA levels were quantified in Scr control, miR-1200, or siBCL11B (SEQ ID NO:4, Table 4) transfected Huh-7 cells. (I) Cells were first transfected with a plasmid expressing luciferase under the control of apoAI promoter and then transfected with miR-1200 or Scr. The luciferase activities were determined after 48 h. (J) Proposed working model: Under normal conditions, BCL11B binds to the apoAI promoter to repress transcription. In miR-1200 overexpressing cells, miR-1200 decreases mRNA levels of BCL11B leading to de-repression of apoAI transcription and increases in mRNA levels. Data are represented as mean±SD. p&lt;0.05, ** P&lt;0.01 and *** P&lt;0.001. 
         FIGS. 4A-4H  show that MiR-1200 differentially regulates HDL and non-HDL cholesterol levels in diet induced hyperlipidemic mice. Male C57BL/6 mice were fed a Western diet for 6 weeks and injected retro-orbitally with miR-1200 or PBS (n=5). Plasma samples were collected 4 days after each injection. (A) A schematic diagram showing amounts of miR injected (top) and times of blood collected (bottom). (B) miR-1200 levels were quantified in different tissues of miR-1200 injected mice and normalized to levels in the small intestine (SI) where the lowest amounts were found. (C) Injection of miR-1200 did not change the expression levels of another endogenous miR, miR-30c, compared to PBS group. (D) Hepatic mRNA levels of different target and non-target genes were quantified in two groups of mice. (E-F) Temporal changes in indicated plasma constituents. (G) Western blot analysis of plasma apolipoproteins and their quantifications by ImageJ. (H) Plasma samples from each group were pooled and subjected to FPLC. Distribution of lipids in different lipoproteins is shown. Data are represented as mean±SD. p&lt;0.05, ** P&lt;0.01 and *** P&lt;0.001. Data are representative of 3 independent experiments. 
         FIGS. 5A-5H  show that MiR-1200 enhances fatty acid oxidation. (A) Hepatic cholesterol and triglyceride were measured in liver homogenates from  FIG. 4 . (B) Liver slices from  FIG. 4  were used to measure fatty acid oxidation and syntheses of fatty acids, triglycerides and phospholipids. (C) Gene expression changes in the livers of mice injected with miR-1200 and PBS. (D) Predicted interaction sites of miR-1200 in the 3′-UTRs of human and mouse NCOR1 mRNA. (E) Huh-7 cells were transfected with 50 nM of miR-1200 or Scr control. After 48 hours, FAO and syntheses of lipids were measured. (F) The mRNA levels of NCOR1 in miR-1200 transfected Huh-7 cells. (G) Huh-7 cells were co-transfected with indicated different siRNA and miRs (50 nM each) to test their effects on fatty acid oxidation. (H) Proposed working model: Under normal conditions, NCOR1 interacts with PPARa/RXR heterodimer (PPARa) to reduce the expression of genes involved in FAO. In miR-1200 overexpressing cells, NCOR1 expression will be reduced resulting in its dissociation from PPARa and allowing the binding of PGC1a to increase the expression of genes involved in FAO. Data are represented as mean±SD. p&lt;0.05, ** P&lt;0.01 and *** P&lt;0.001. 
         FIGS. 6A-6E  show that MiR-1200 decreases VLDL production and promotes reverse cholesterol transport. Male C57B1/J mice were fed on a Western diet for 6 weeks and then injected with 1 mg/kg/week of miR-1200 or PBS (n=7). (A) Time course of plasma lipid levels. (B) Four days after the third injection, mice were divided into two groups. In one group, mice were fasted for 18 hours and injected with Poloxamer 407 and [ 35 S] Promix to study VLDL production (n=3). Time dependent changes in plasma triglyceride were measured. (C) apoB was immunoprecipitated from plasma samples obtained from 2 hour time points and visualized by autoradiography (left). apoB bands were quantified with ImageJ (right). Amounts of newly secreted apoAI were too low to detect. (D) Mice in the second group were intraperitoneally injected with  3 H-cholesterol labeled and Ac-LDL loaded J774.1A macrophages (n=4). Radioactivity was measured in plasma, feces, and livers after 48 hours to assess reverse cholesterol transport (RCT). (E) J774A.1 macrophages were loaded with  3 H-cholesterol and Ac-LDL and used for 6 h cholesterol efflux studies. Left: Plasma samples (5%) from PBS or miR-1200 treated C57BL/6J mice from  FIG. 4  were used for cholesterol efflux (n=5). Right: Isolated HDL (5%) was used as cholesterol acceptor. Data are represented as mean±SD. p&lt;0.05, ** P&lt;0.01 and *** P&lt;0.001. 
         FIGS. 7A-7H  show that MiR-1200 reduces plasma cholesterol and atherosclerosis in Apoe −/−  mice. Western diet fed male Apoe −/−  mice were injected with 2 mg/kg/week of miR-1200 or PBS (n=5). (A) Quantification of miR-1200 in different organs and hepatic miR-30c levels. (B) Hepatic expression levels of target and non-target genes. (C) Temporal changes in total plasma cholesterol, phospholipid, and triglyceride. (D) Plasma samples from each group were pooled and fractionated by FPLC. Cholesterol, phospholipid and triglyceride were measured in each fraction. The inserts show amplified HDL peaks. (E) Plasma AST, ALT, and CK activities were measured at the end. (F) Livers from two groups were used for hepatic lipids quantification. (G) Aortic arches were exposed, photographed and quantified. (H) Aortas were isolated, fixed and stained with Oil Red O. ImageJ was used for quantification of the atherosclerotic lesions. Data are represented as mean±SD. p&lt;0.05, ** P&lt;0.01 and *** P&lt;0.001. 
         FIG. 8  provides a graphical summary of miR-1200 regulation 
         FIG. 9  shows that Hsa-miR-1200 is present in the intron of ELMO1 and is conserved in primates. The top line shows schematic representation of different introns and exons in the human ELMO1 gene. MiR-1200 resides in intron 6 of the gene. Pre-miR-1200 sequences are highly conserved in primates and are highlighted with gray after alignment using Clustal W. 
         FIG. 10  shows: (top) predicted base-pairing at four different sites between miR-1200 and the 3′-UTR of human BCL11B; (bottom) three miR-1200 target sites on BCL11B 3′-UTR that are well conserved in different species. MiRanda was used to predict potential targets of miR-1200. 
         FIGS. 11A-11C  show that (A-B) MiR-1200 regulates apoB and apoAI in HepG2 cells. Human hepatoma HepG2 cells were reverse transfected with miRs [50 nM]. NT: non-transfected. Media and cellular apolipoproteins were measured after 48 hours. (C) Effect of miR-1200 on mRNA levels in mouse hepatoma AML12 cells. AML 12 cells were plated and were forward transfected with miR-1200 and Scr control [50 nM] using Lipofectamine RNAiMAX. Expression levels of indicated genes were quantified after 48 hours. 
         FIGS. 12A-12E  show that miR-1200 reduces plasma cholesterol and atherosclerosis in Apoe−/− mice without causing liver injury. Male Apoe−/− mice were fed a Western diet for 6 weeks and then injected with 1 mg/kg/week of miR-1200 or PBS control (n=3). Plasma samples were collected four days after each injection. (A) Hepatic expression levels of target and non-target genes. (B) Hepatic cholesterol and triglyceride levels were measured. (C) Time course of total plasma cholesterol. (D) Time course of changes in plasma triglyceride, ALT, AST, and CK activities. (E) Aortas were isolated, fixed and stained with Oil Red 0. Image J was used to quantify the lesion size. 
     
    
    
     DETAILED DESCRIPTION 
     Despite significant advances in lowering risk factors, cardiovascular diseases (CVD) accounted for 30.8% of deaths in 2003-2013 in the United States, and the estimated annual cost of CVD and stroke for 2011-2012 was about $316.6 billion. Most of the risk factors for CVD are controllable, especially plasma cholesterol, which is carried in the blood by apolipoprotein B (apoB)-containing lipoproteins, such as low-density lipoproteins (LDLs), and non-apoB-containing high-density lipoproteins (HDLs). apoB-containing lipoproteins are primarily synthesized and secreted by the liver and small intestine to transport lipids to other peripheral tissues. Excess accumulation of these lipoproteins and their modifications in the plasma contribute to atherosclerosis as these modified lipoproteins are taken up by macrophages. apoAI interacts with ATP-binding cassette transporter family A and protein 1 (ABCA1) present on the plasma membrane of different cells, especially macrophages, extracts cholesterol and transports it back to the liver for excretion from the body. This reverse cholesterol transport (RCT) is believed to be anti-atherogenic. For these reasons, elevated LDL and low HDL are two well-established risk factors for atherosclerosis. 
     Statins lower plasma LDL-cholesterol by reducing hepatic cholesterol synthesis and increasing LDL clearance. However, these drugs only decrease the incidence of cholesterol related diseases by 30-40%, and almost 20% of the population fails to respond to or cannot tolerate statins. Further, high doses of statins sometimes cause muscle pain, elevations in plasma levels of liver and muscle enzymes, and new onset of diabetes mellitus. 
     While PCSK9 inhibitors have been shown to lower plasma cholesterol, PCSK9 inhibitors have also been associated with neurocognitive side effects. Because the target of both statins and PCSK9 inhibitors is the LDL receptor, these drug classes are not useful in the treatment of homozygous familial hypercholesterolemia subjects that are deficient in this receptor. Prior to the subject technology, no effective therapeutic methods were available to increase functional HDL to prevent CVD. Thus, a need remains for novel therapeutic agents that modulate plasma LDL and HDL to achieve therapeutically beneficial outcomes. 
     Other known methods for reducing LDL include total plasma exchange (TPE) and LDL apheresis. TPE replaces all plasma every 7-14 days and can reduce plasma LDL to below target levels. HDL levels are also severely reduced however, and the sharp decrease in LDL is followed by a rebound phase as new VLDL is synthesized and secreted. LDL apheresis is similar in that it selectively removes apoB containing lipoproteins, but unlike TPE, LDL apheresis spares HDL. The side effects for both procedures, however, include hypotension, anemia, and hypocalcaemia. Moreover, these treatments are time consuming, invasive and not universally available. 
     In severe cases, liver transplantation may also be a viable option to lower lipid levels and prevent early onset cardiac events. Liver transplantation is however costly, not readily available globally, and limited by the availability of suitable donors. 
     MicroRNAs (miRs) are small (˜22 nucleotides) non-coding RNAs that target multiple genes and affect multiple pathways by interacting with the 3′-untranslated region (3′-UTR) of mRNA and destabilizing mRNA or blocking translation. In &gt;70% of cases, miRs mediate regulation by mRNA degradation. MiRs bind to the target mRNA via seed and supplementary sequences. A seed sequence (2-7 nucleotides from the 5′-end of the miR) forms perfect complementary base pairs, while the supplementary site in the 3′-region may or may not form perfect base pairs with the target mRNA. MiRs with the same seed sequence belong to the same family. MiR-30c and miR-33 have been identified to decrease LDL and HDL, respectively, and MiR-148a consistently decreased HDL but had variable effects on plasma LDL levels. However, no MiR has previously been shown to both decrease LDL and increase HDL. 
     High plasma LDL and low HDL cholesterol levels are risk factors for cardiovascular diseases. Although therapeutics would ideally both lower LDL and increase HDL, there were no known drug therapies that concomitantly mitigate these risk factors prior to the subject technology. Moreover, existing therapeutics such as statins and PCSK9 inhibitors are only partially effective and can cause serious adverse effects. 
     The subject technology provides methods of administering a miR comprising SEQ ID NO:1, wherein the miR decreases apoB and increases apoAI in a mammal, resulting in lower levels of LDL and higher levels of HDL in plasma. 
     In some embodiments of the subject technology, the miR comprises a sequence with at least 70%, 75%, 80%, 85%, 90% or 95% identity to SEQ ID NO:2. In certain embodiments, the miR is miR-1200, and has the sequence of SEQ ID NO:2. (See Table 1.) 
     The subject technology provides methods of simultaneously lowering plasma LDL and increasing plasma HDL. In some embodiments of the subject technology, a microRNA comprising SEQ ID NO:1 is administered to a mammal, wherein the microRNA reduces plasma LDL and increases plasma HDL via different mechanisms, thus mitigating dyslipidemia and atherosclerosis. In some embodiments, the microRNA is miR-1200. 
     The subject technology includes methods of significantly reducing apoB (an LDL structural protein) while increasing apoAI (main HDL protein) secretion. In some embodiment, the methods reduce apoB while increasing apoAI in cell culture. In some embodiments, the methods reduce apoB while increasing apoAI in hepatic or hepatoma cells. In some embodiments, the methods reduce apoB while increasing apoAI in the liver of a human or other mammal. In some aspects of the subject technology, apoB expression is decreased by an inhibitor that causes degradation of mRNA encoding apoB, e.g. the human apoB mRNA (Gene accession NM_000384, Appendix A). In other aspects of the subject technology, apoAI expression is increased by an inhibitor that causes degradation of mRNA encoding a repressor of ApoAI, such as NRIP1, e.g. human NRIP1 mRNA (Gene accession NM_003489, Appendix A) and/or BCL11B, e.g. human BCL11B mRNA (Gene accession NM_022898, Appendix A). 
     In some embodiments of the subject technology, apoAI is increased by inhibiting its repressor, BCL11B. In some embodiments, BCL11B expression is inhibited by a miR. In yet another embodiment, BCL11B is inhibited by an RNA longer than 20 nucleotides, such as an RNA that is longer than 30, 50, 75, 100, 125 or 200 nucleotides. In another embodiment, BCL11B is inhibited by a nucleic acid comprising modified nucleotides, a double-stranded nucleic acid inhibitor, a protein inhibitor or a small molecule inhibitor. 
     In some embodiments of the subject technology, apoAI is increased by inhibiting its transcriptional repressor, NRIP1. In some embodiments, NRIP1 expression is inhibited by an siRNA. In yet another embodiment, NRIP1 is inhibited by an RNA longer than 20 nucleotides, such as an RNA that is longer than 30, 50, 75, 100, 125 or 200 nucleotides. In another embodiment, NRIP1 is inhibited by a nucleic acid comprising modified nucleotides, a double-stranded nucleic acid inhibitor, a protein inhibitor or by a small molecule inhibitor. In some embodiments, NRIP1 inhibitors are administered to an animal or human, alone or in combination with inhibitors of BCL11B and/or apoB, to achieve a therapeutically effective result, such as treating or preventing hyperlipidemia and/or atherosclerosis. 
     A microRNA is a short RNA. MicroRNAs may also be denoted miRNA or miR herein. Preferably a miRNA to be used with the subject technology is 19-25 nucleotides in length and consists of non-protein-coding RNA. Mature miRNAs may exert, together with the RNA-induced silencing complex, a regulatory effect on protein synthesis at the post-transcriptional level. More than 1500 human miRNA sequences have been discovered to date and their names and sequences are available from the miRBase database (http://www.mirbase.org). 
     A miRNA of the subject technology can be synthesized, altered, or removed from the natural state using a number of standard techniques known in the art. A synthetic miRNA, or a miRNA partially or completely separated from its coexisting materials is considered isolated. An isolated miRNA can exist in substantially purified form, or can exist in a cell into which the miRNA has been delivered. A miRNA can be chemically synthesized using appropriately protected ribonucleoside phosphoramidites and a conventional DNA/RNA synthesizer. Commercial suppliers of synthetic RNA molecules or synthesis reagents include, e.g., Proligo (Hamburg, Germany), Dharmacon Research (Lafayette, Colo., USA), Rosetta Genomics (North Brunswick, N.J.), Pierce Chemical (part of Perbio Science, Rockford, Ill., USA), Glen Research (Sterling, Va., USA), ChemGenes (Ashland, Mass., USA), Ambion (Foster City, Calif., USA), and Cruachem (Glasgow, UK). 
     In some embodiments, the miRs of the invention are delivered to target cells using an expression vector encoding the miR. A variety of suitable vectors are known in the art, including plasmids, viruses, and linear polynucleotides. Plasmids suitable for expressing any of the miRs of the subject technology, methods for inserting nucleic acid sequences into the plasmid to express the miR of interest, and methods of delivering the recombinant plasmid to cells of interest are well established and practiced in the art. Examples of suitable plasmids and methods of expression and delivery can be found in Zeng et al. (2002),  Molecular Cell  9:1327-1333; Tuschl (2002),  Nat. Biotechnol,  20:446-448; Brummelkamp et al. (2002),  Science  296:550-553; Miyagishi et al. (2002),  Nat. Biotechnol.  20:497-500; Paddison et al. (2002),  Genes Dev.  16:948-958; Lee et al. (2002),  Nat. Biotechnol.  20:500-505; and Paul et al. (2002),  Nat. Biotechnol.  20:505-508, the entire disclosures of which are herein incorporated by reference. 
     In other embodiments, the miRs of the subject technology are expressed from recombinant viral vectors. Non-limiting examples of viral vectors include retroviral vectors, adenoviral vectors (AV), adeno-associated virus vectors (AAV), herpes virus vectors, and the like. Recombinant viral vectors suitable for expressing miRs of the subject technology, methods for inserting nucleic acid sequences for expressing RNA in the vector, methods of delivering the viral vector to cells of interest, and recovery of the expressed RNA molecules are within the skill in the art. Examples include Dornburg (1995),  Gene Therap.  2:301-310; Eglitis (1988),  Biotechniques  6:608-614; Miller (1990),  Hum. Gene Therap.  1:5-14; and Anderson (1998),  Nature  392:25-30, the entire disclosures of which are herein incorporated by reference. 
     Various modifications to the miRs of the subject technology can be introduced as a means of increasing intracellular stability, therapeutic efficacy, and shelf life. Some modifications include but are not limited to the addition of flanking sequences of ribonucleotides or deoxyribonucleotides to the 5′ and/or 3′ ends of the molecule, or the use of phosphorothioate or 2′-O-methyl rather than phosphodiesterase linkages within the oligonucleotide backbone. 
     In yet other embodiments, the miRs of the subject technology are expressed from recombinant circular or linear plasmids using any suitable promoter. Selection of suitable promoters is within the skill in the art. Suitable promoters include but are not limited to U6 or H1 RNA pol III promoter sequences or cytomegalovirus promoters. Recombinant plasmids can also comprise inducible or regulatable promoters for miRNA expression in cells. For example, the CMV intermediate-early promoter may be used with the miRNAs of the subject technology to initiate transcription of the miRNA gene product coding sequences. 
     A further embodiment of the subject technology provides a method of preventing or treating a disease associated with high apoB and/or low apoAI levels, including but not limited to insulin resistance, type II diabetes, schizophrenia, fatty liver disease, inflammation, hepatitis C, familial hypercholesterolemia, and rheumatoid arthritis. 
     An additional embodiment of the subject technology provides a method of preventing or treating a disease associated with reduced LDL and increased HDL, including but not limited to cardiovascular disease (coronary artery disease, peripheral arterial disease, cerebral vascular disease, cardiomyopathy, hypertensive heart disease, cardiac dysrhythmias, inflammatory heart disease, aortic aneurysm, renal artery stenosis, valvular heart disease), atherosclerosis, fatty liver disease, diabetic dyslipidemia, and hypocholesterolemia. 
     In one embodiment, the subject technology features changing levels of apoB, apoAI, HDL, and/or LDL with a microRNA administered with additional agents at a therapeutically effective amount. The term “therapeutically effective amount,” as used herein, refers to the total amount of microRNA and each additional agent that is sufficient to show a meaningful benefit to the subject. 
     Pharmaceutical compositions of the subject technology can also comprise conventional pharmaceutical excipients and/or additives. Suitable pharmaceutical excipients include stabilizers, antioxidants, osmolality adjusting agents, buffers, and pH adjusting agents. Suitable additives include physiologically biocompatible buffers (e.g., tromethamine hydrochloride), additions of chelants (such as, for example, DTPA or DTPA-bisamide) or calcium chelate complexes (as for example calcium DTPA, CaNaDTPA-bisamide), or calcium or sodium salts (for example, calcium chloride, calcium ascorbate, calcium gluconate or calcium lactate). 
     Delivery of the compositions in the claimed methods may be facilitated by use of a biocompatible gel, a lipid-based delivery system, such as liposomes, polycationic liposome-hyaluronic acid (LPH) nanoparticles (Medina, 2004), LPH nanoparticle conjugated to a peptide, such as an integrin-binding peptide (Liu, 2011), cationic polyurethanes such as polyurethane-short branch-polyethylenimine (PU-PEI), a glycoprotein-disulfide linked nanocarrier (Chiou, 2012) or other known miR delivery systems including, but not limited to dendrimers, poly(lactide-co-glycolide) (PLGA) particles, protamine, naturally occurring polymers, (e.g. chitosan, protamine, atelocollagen), peptides derived from protein translocation domains, inorganic particles, such as gold particles, silica-based nanoparticles, or magnetic particles. (Zhang, 2013). 
     If desired, the miRs of the subject technology may be modified to protect against degradation, improve half-life, or to otherwise improve efficacy. Suitable modifications are described, e.g. in U.S. Patent Publication Nos. 20070213292, 20060287260, 20060035254, 20060008822, and 20050288244, each of which is hereby incorporated by reference in its entirety. 
     Pharmaceutical compositions of the subject technology can be packaged for use in liquid or solid form, or can be lyophilized. Conventional nontoxic solid pharmaceutically-acceptable carriers can be used for solid pharmaceutical compositions of the subject technology. Examples of carriers include but are not limited to pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, talcum, cellulose, glucose, sucrose, and magnesium carbonate. 
     Pharmaceutical formulations may be adapted for administration by any appropriate route. For example, appropriate routes may include oral, nasal, topical (including buccal, sublingual, or transdermal), or parenteral (including subcutaneous, intrasternal, intracutaneous, intramuscular, intraarticular, intraperitoneal, intrasynovial, intrathecal, intralesional, intravenous, intradermal injections or infusions). For human administration, the formulations preferably meet sterility, pyrogenicity, general safety, and purity standards, as required by the offices of the Food and Drug Administration (FDA). 
     The therapeutically effective amount of microRNA varies depending on several factors, such as the condition being treated, the severity of the condition, the time of administration, the duration of treatment, the age, gender, weight, and condition of the subject. In some embodiments of the subject technology, a therapeutically effective amount of miR comprising SEQ ID NO:1 for treatment of a human is 0.1-2 mg/kg/week. In some of these embodiments, the therapeutically effective amount is 0.1-0.5 mg/kg/week, 0.5-1 mg/kg/week, 1-1.5 mg/kg/week, 1.5-2 mg/kg/week, 0.1 mg/kg/week, 1 mg/kg/week, 1.5 mg/kg/week or 2 mg/kg/week. A person of ordinary skill in the art would understand that this initial dose can be adjusted based on the severity and type of condition being treated, the mode of administration and the response of the individual patient. One of ordinary skill in the art may also modify the route of administration in order to obtain the maximal therapeutic effect. Where a dosage regimen comprises multiple administrations, the effective amount of the miRNA molecule administered to the subject can comprise the total amount of gene product administered over the entire dosage regimen. 
     The microRNA in the subject technology can be administered with additional agents in combination therapy, either jointly or separately, or by combining the microRNA and additional agents(s) into one composition. 
     For example, the miRNA pharmaceutical compositions of the subject technology can be used to treat hypercholesterolemia or atherosclerosis, either alone or in combination with a statin. Examples of statins include Atorvastatin (Lipitor), Ezetimibe/Simvastatin (Vytorin), Lovastatin (Mevacor), Simvastatin (Zocor), Pravastatin (Pravachol), Fluvastatin (Lescol), and Rosuvastatin (Crestor), Fenofibrate (Lipofen), Gemfibrozol (Lopid) and/or Ezetimibe (Zetia). 
     In other embodiments, the pharmaceutical compositions of the subject technology are administered in combination with ACE inhibitors, aldosterone inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, calcium channel blockers, cholesterol lowering drugs, digoxin, diuretics, inotropic therapy, potassium or magnesium, PCSK9 inhibitors (otherwise known as monoclonal antibodies), vasodilators, or warfarin. 
     Examples of ACE inhibitors include but are not limited to Accupril (quinapril), Aceon (perindopril), Altace (ramipril), Capoten (captopril), Lotensin (benazepril), Mavik (trandolapril), Monopril (fosinopril), Prinivil, Zestril (lisinopril), Univasc (moexipril), and Vasotec (enalapril). 
     Examples of aldosterone inhibitors include but are not limited to eplernone (Inspra) and spironolactone (Aldoctone). 
     Examples of angiotensin II receptor blockers (ARBs) include but are not limited to candesartan (Atacand), eprosartan (Teventen), irbesartan (Avapro), Iosartan (Cozar), telmisartan (Micardis), valsartan (Diovan), and olmesartan (Benicar). 
     Examples of beta-blockers include acebutolol hydrochloride (Sectral), atenolol (Tenormin), betaxolol hydrochloride (Kerlone), bisoprolol fumarate (Zebeta), carteolol hydrochloride (Cartrol), esmolol hydrochloride (Brevibloc), metoprolol (Lopressor, Toprol XL), and penbutolol sulfate (Levatol). 
     Examples of calcium channel blockers include Amlodipine (Norvasc), Diltiazem (Cardizem, Tiazac), Felodipine, Isradipine, Nicardipine (Cardene SR), Nifedipine (Procardia) Nisoldipine (Sular), and Verapamil (Calan, Verelan, Covera-HS). 
     The practice of aspects of the subject technology can employ, unless otherwise indicated, conventional techniques of cell biology, cell culture, molecular biology, transgenic biology, microbiology, recombinant DNA, and immunology, which are within the skill of the art. These techniques are fully explained in literature. Examples of conventional techniques can be found in Molecular Cloning: A Laboratory Manual, 2nd Ed., ed. by Sambrook, Fritsch and Maniatis (Cold Spring Harbor Laboratory Press: 1989); DNA Cloning, Volumes I and II (D. N. Glover ed., 1985); Oligonucleotide Synthesis (M. J. Gait ed., 1984); Mullis et al. U.S. Pat. No: 4,683,195; Nucleic Acid Hybridization (B. D. Hames &amp; S. J. Higgins eds. 1984); Transcription And Translation (B. D. Hames &amp; S. J. Higgins eds. 1984); Culture Of Animal Cells (R. I. Freshney, Alan R. Liss, Inc., 1987); Immobilized Cells And Enzymes (IRL Press, 1986); B. Perbal, A Practical Guide To Molecular Cloning (1984); the treatise, Methods In Enzymology (Academic Press, Inc., N.Y.); Gene Transfer Vectors For Mammalian Cells (J. H. Miller and M. P. Calos eds., 1987, Cold Spring Harbor Laboratory); Methods In Enzymology, Vols. 154 and 155 (Wu et al. eds.), Immunochemical Methods In Cell And Molecular Biology (Mayer and Walker, eds., Academic Press, London, 1987); Handbook Of Experimental Immunology, Volumes I-IV (D. M. Weir and C. C. Blackwell, eds., 1986); and Manipulating the Mouse Embryo, (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1986). All patents, patent applications and references cited herein are incorporated in their entirety by reference. 
     EXAMPLES 
     The following specific examples are to be construed as merely illustrative, and not limiting the remainder of the disclosure in any way. It is believed that one skilled in the art can, based on the description herein, utilize the subject technology to its fullest extent. 
     Example 1 
     Identification of MicroRNAs Regulating apoB and apoAI Secretion from Human Hepatoma Cells 
     To identify miRs regulating apoB and apoAI secretion, human hepatoma Huh-7 cells were transfected with 1237 human miRs (human miRIDIAN Mimic 16.0 library, Dharmacon). 
     MiRs were suspended in RNase free water to obtain 2 μM stocks and 3 μL of each miR was added in duplicate wells to obtain a final concentration of 50 nM. 7 μl of Opti-MEM and 10 μl of lipofectamine RNAiMAX (Life technologies) diluted 1:20 in Serum Reduced Opti-MEM was added to each well. After 20 to 30 minutes, 25,000 cells in 100 μl of Opti-MEM were added to each well. After additional 24 hours, culture media were changed with fresh DMEM containing 10% fetal bovine serum. Media were changed 24 hours later and cells were incubated with DMEM containing oleic acid/BSA complex ((oleic acid (0.4 mM)/BSA (1.5%)) for 2 hours. 
     apoB and apoAI concentrations in medium were measured by ELISA (Hussain et al., 1995). Secreted apolipoproteins were quantified by ELISA as shown in  FIG. 1A . For intracellular apoB measurement, cells were homogenized in 100 mM Tris buffer (pH7.4) containing 150 mM NaCl, 1 mM EGTA, 1 mM EDTA, 1% Triton X-100 and 0.5% SDS. apoB was measured via ELISA (Walsh et al., 2015). 
     The first screening performed in duplicate plates showed high reproducibility (Spearman r=0.96 and 0.92;  FIG. 1B ) and resulted in the identification of 60 and 57 miRs that decreased and increased, respectively, apoB secretion by over 50%; and 34 and 38 miRs that decreased and increased apoAI secretion by over 35% ( FIG. 1C ). Within these miRs, miRs in the same families exhibited similar effects on apoB and apoAI secretion indicating good internal reproducibility ( FIG. 1D ). In the second screening of 102 candidate miRs, 75 miRs gave results similar to the first screening. miR-1200 decreased apoB secretion by 61±2%, and increased apoAI secretion by 54±17%. 
     Example 2 
     MiR-1200 Decreases apoB Secretion by Enhancing Posttranscriptional mRNA Degradation 
     Hsa-miR-1200 is located in the 6 th  intron of Engulfment and cell motility protein 1 (ELMO1) on human chromosome 7, and the precursor miR-1200 is conserved ( FIG. 9 ). To study its role, Huh-7 cells were transfected with miR-1200 to increase cellular concentrations ( FIG. 2A ). MiR-1200 decreased media and cellular apoB in a dose-dependent manner ( FIGS. 2B, 2C ). Hairpin inhibitor of miR-1200, anti-1200, dose-dependently increased apoB suggesting that endogenous miR-1200 regulates apoB production ( FIGS. 2B, 2C ). The effects of miR-1200 and anti-1200 on cellular and media were maximum at 48 hours post transfection ( FIGS. 2D, 2E ). These studies showed that miR-1200 reduces, whereas anti-1200 increases, cellular and media apoB. 
     Lower cellular apoB protein levels could be due to reductions in mRNA or protein synthesis. Quantifications revealed that apoB mRNA levels were reduced in miR-1200 and increased in anti-1200 over-expressing cells, suggesting that miR-1200 modulates mRNA levels ( FIG. 2F ). To investigate how miR-1200 reduces apoB mRNA, mRNA degradation was determined after treating cells with actinomycin D to inhibit transcription. apoB mRNA disappeared faster in miR-1200 expressing cells ( FIG. 2G ), indicating that miR-1200 enhances posttranscriptional degradation. mRNA half-life was measured as follows: Huh-7 cells (1.2*10 5 /well) in 12-well plates were reverse transfected with miR-1200 or Scr (50 nM). After 24 hours, cells were treated with 1 μg/mL actinomycin D in growth medium. Total RNA were collected at different time points to quantify mRNA levels by qRT-PCR Primers used for qRT-PCR are shown in Table 2. 
     RNA isolation and qRT-PCR: Total RNA from tissues and cells was extracted using TRIzol (Invitrogen). RNA was reverse transcribed into cDNA with the Omniscript RT kit (QIAGEN). Expression levels of gene are quantified by qRT-PCR using SYBER Green qPCR Core Kit (Eurogentec), and data was analyzed with ΔΔCT method and normalized to 18S. Primers specific for miR-1200, miR-30c, snoRNA 202 were purchased from Life Technologies. 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Primers used for quantitative PCR 
               
            
           
           
               
               
               
            
               
                 Gene 
                 Forward primer 
                 Reverse primer 
               
               
                   
               
               
                 Human apoAI 
                 5′-GCAGAGACTATGTGTCCCAGTTTG-3′ 
                 5′-CCAGTTGTCAAGGAGCTTTAG-3′ 
               
               
                   
               
               
                 Human apoB 
                 5′-TGACCTTGTCCAGTGAAGTC-3′ 
                 5′-GTTCTGAATGTCCAGGGTGA-3′ 
               
               
                   
               
               
                 Human ABCA1 
                 5′-TGGTCTCCAAGCAGAGTGTG-3′ 
                 5′-GAGCAGCAGCTCCCAATAC-3′ 
               
               
                   
               
               
                 Human BCL11B 
                 5′-CACCCCCGACGAAGATGACCAC-3′ 
                 5′-CGGCCCGGGCTCCAGGTAGATG-3′ 
               
               
                   
               
               
                 Human NCOR1 
                 5′-CTGACAGGCCTCAAGAAAGG-3′ 
                 5′-AACCTGTTCCAGACGTGGTC-3′ 
               
               
                   
               
               
                 Mouse apoAI 
                 5′-GGCCGTGGCTCTGGTCTT-3′ 
                 5′-GGTTCATCTTGCTGCCATACC-3′ 
               
               
                   
               
               
                 Mouse apoB 
                 5′-CTCGACCATCGGCACTGT-3′ 
                 5′-AGTTTCTTCTCTGGAGGGGACT-3′ 
               
               
                   
               
               
                 Mouse MTP 
                 5′-CACACAACTGGCCTCTCATTAAAT-3′ 
                 5′-TGCCCCCATCAAGAAACACT-3′ 
               
               
                   
               
               
                 Mouse ABCA1 
                 5′-TTGGCGCTCAACTTTTACGAA-3′ 
                 5′-GAGCGAATGTCCTTCCCCA-3′ 
               
               
                   
               
               
                 Mouse BCL11B 
                 5′-GAGCCCTTTCCAGCTCTCTT-3′ 
                 5′-CCAGGTCTTTCTCCACCTTG-3′ 
               
               
                   
               
               
                 Mouse ABCG1 
                 5′-ACAACTTCACAGAGGCCCAG-3′ 
                 5′-TTTCCCAGAGATCCCTTTCA-3′ 
               
               
                   
               
               
                 Mouse SR-BI 
                 5′-ACGGCCAGAAGCCAGTAGTC-3′ 
                 5′-GACCTTTTGTCTGAACTCCCTGTAG-3′ 
               
               
                   
               
               
                 Mouse NCOR1 
                 5′-AGAACTTCTGATGTTTCTTCCAG-3′ 
                 5′-CTGGAGACTTGGCTGGTATA-3′ 
               
               
                   
               
               
                 Mouse CPT1A 
                 5′-AAGCACCAGCACCTGTACCG-3′ 
                 5′-CCTTTACAGTGTCCATCCTCTG-3′ 
               
               
                   
               
               
                 Mouse ACOX1 
                 5′-AAGAGTTCATTCTCAACAGCCC-3′ 
                 5′-CTTGGACAGACTCTGAGCTGC-3′ 
               
               
                   
               
               
                 Mouse MCAD 
                 5′-TTACCGAAGAGTTGGCGTATG-3′ 
                 5′-ATCTTCTGGCCGTTGATAACA-3′ 
               
               
                   
               
               
                 Mouse PGC-1a 
                 5′-ATACCGCAAAGAGCACGAGAAG-3′ 
                 5′-CTCAAGAGCAGCGAAAGCGTCACAG-3′ 
               
               
                   
               
               
                 18s rRNA 
                 5′-AGTCCCTTGCCCTTTGTACACA-3′ 
                 5′-GATCCGAGGGCCTCACTAAAC-3′ 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 3 
               
               
                   
               
               
                 Primers used for site-directed mutagenesis 
               
               
                   
               
             
            
               
                 apoB  C231G _A232G_G233C 
               
               
                 Forward: 5′-TAGCAAAATAACTCAGATCGCCATTTTCTTTAACTTGCAAAAAATGCCATCCTTCTG-3′ 
               
               
                   
               
               
                 Reverse: 5′-CAGAAGGATGGCATTTTTTGCAAGTTAAAGAAAATGGCGATCTGAGTTATTTTGCTA-3′ 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 siRNAs (Dharmacon) 
               
            
           
           
               
               
               
               
            
               
                 Catalog 
                 Gene 
                 Gene 
                   
               
               
                 Number 
                 Symbol 
                 Accession 
                 Sequence 
               
               
                   
               
               
                 D-006686- 
                 NRIP1 
                 NM_003489 
                 SEQ ID NO: 3: 
               
               
                 01 
                   
                   
                 GAACAAAGGUCAUGAGUGA 
               
               
                   
               
               
                 D-005082- 
                 BCL11B 
                 NM_022898 
                 SEQ ID NO: 4: 
               
               
                 01 
                   
                   
                 GAGCAAGUCGUGCGAGUUC 
               
               
                   
               
               
                 D-020818- 
                 ZBTB7A 
                 NM_015898 
                 SEQ ID NO: 5: 
               
               
                 01 
                   
                   
                 UCACCGCGCUCAUGGACUU 
               
               
                   
               
            
           
         
       
     
     The mechanism by which miR-1200 regulates apoB mRNA degradation was further elucidated by in silico analysis using miRanda (http://www.microrna.org/microrna/home.do), showing that apoB mRNA contains a miR-1200 interacting site in its 3′-UTR ( FIG. 2H ). This indicates that miR-1200 interacts with the 3′-UTR of apoB mRNA to increase degradation. DNA encoding the 3′-UTR of human apoB mRNA was inserted after the luciferase cDNA in psiCHECK2 plasmid by standard cloning methods to obtain pLuc-apoB-3′-UTR expression plasmid. This plasmid or control psiCHECK2 plasmid (1.5 μg) was transfected using TurboFect transfection reagent (Dharmacon) in Huh-7 cells (1.2*106) plated in 10 cm Petri dishes one day before transfection. After 24 hours of transfection, cells were detached and plated in 6-well plates containing miRs+RNAiMAX for reverse transfection (final concentration: 50 nM). Luciferase activity was measured after 48 hours with Dual-Luciferase Reporter Assay System (Promega). apoAI promoter luciferase reporter construct was purchased from GeneCopoeia. Luciferase activity of this plasmid was significantly reduced by miR-1200 and this inhibition was avoided after mutagenesis of the complementary site that interacts with the seed sequence ( FIG. 2I ). These results indicate that miR-1200 interacts with the 3′-UTR of apoB to increase mRNA degradation ( FIG. 2J ). 
     Example 3 
     MiR-1200 Increases apoAI Secretion by Reducing BCL11B, a Repressor of apoAI Transcription 
     The following example demonstrates that miR-1200 increases apoAI secretion by reducing BCL11B, a repressor of apoAI transcription. MiR-1200 dose-dependently enhanced apoAI secretion by ˜41% in Huh-7 cells compared to Scr ( FIG. 3A ). Time course studies showed that media apoAI continued to increase until 72 hours after miR-1200 transfection ( FIG. 3B ). MiR-1200 increased apoAI mRNA by ˜6-fold ( FIG. 3C ). Therefore, overexpression of miR-1200 increases media apoAI by elevating mRNA levels. In these studies, anti-1200 had no effect on apoAI expression ( FIGS. 3A-C ) indicating a complex mode of apoAI regulation different from that of apoB. MiR-1200 had no effect on apoAI mRNA degradation ( FIG. 3D ). However, it increased the activity of a 1.2 kb apoAI promoter by ˜67% ( FIG. 3E ) demonstrating that miR-1200 increases apoAI mRNA by enhancing transcription. 
     Although miRs normally reduce gene expression (He and Hannon, 2004), they have been shown to activate transcription by interacting with promoter sequences involving complementary base pairing via RNA activation (Huang et al., 2012; Place et al., 2008). There were no miR-1200 complementary sequences in the 1.2-kb apoAI promoter. To determine whether miR-1200 may instead increase apoAI transcription by suppressing a transcriptional repressor(s), three transcriptional repressors were selected from a list of predicted miR-1200 target genes generated by TargetScan (http://www.targetscan.org/) as they had the potential to bind the apoAI promoter, and the target sites were conserved in human and mouse. Huh-7 cells were then transfected with siRNAs against NRIP1 (Nuclear Receptor Interacting Protein 1), BCL11B (B-Cell Lymphoma 11B), or ZBTB7A (Zinc Finger and BTB Domain Containing 7A) ( FIG. 3F ). As expected, miR-1200 reduced apoB; however siNRIP1 (SEQ ID NO:3, Table 4) increased apoB secretion while siBCL11B and siZBTB7A had no effect on apoB indicating that these repressors do not regulate apoB secretion like miR-1200. However, similar to miR-1200, both siNRIP1 and siBCL11B increased media apoAI by about ˜46-53%, but siZBTB7A had no effect. Therefore, NRIP1 and BCL11B may work as apoAI repressors. 
     To test whether BCL11B is an intermediary in the regulation of apoAI by miR-1200, miR-1200 was co-transfected with siRNAs in Huh-7 cells ( FIG. 3G ). MiR-1200 and siNRIP1 alone increased apoAI secretion by 64 and 50%, respectively, while a combination of both miR-1200 and siNRIP1 increased apoAI secretion by 104% compared to Scr+siControl. This suggests that NRIP1 and miR-1200 additively increase apoAI secretion by possibly involving two independent mechanisms ( FIG. 3G ). On the other hand, miR-1200, siBCL11B and siBCL11B+miR-1200 increased apoAI to similar levels ( FIG. 3G ). In contrast, miR-1200 reduced apoB secretion in cells treated with both siNRIP1 and siBCL1B. These data show that miR-1200 is unable to increase apoAI secretion in siBCL11B treated cells but is able to reduce apoB secretion. Thus, miR-1200 increases apoAI expression indirectly by reducing expression of its repressor, BCL11B. 
     Bioinformatics analyses showed that the 3′-UTR of the human BCL11B mRNA contained 4 miR-1200 binding sites and 3 of these sites were evolutionarily conserved ( FIG. 10 ). To test whether miR-1200 regulates BCL11B, mRNA levels were quantified in miR-1200 transfected cells. BCL11B mRNA levels were decreased by ˜56% in miR-1200 and siBCL11B expressing cells ( FIG. 3H ), indicating that miR-1200 regulates BCL11B expression. Further, siBCL11B increased apoAI promoter activity by ˜2.6-fold ( FIG. 3I ), suggesting that BCL11B represses apoAI transcription. These studies indicate that miR-1200 increases apoAI expression by reducing BCL11B ( FIG. 3J ). 
     Example 4 
     MiR-1200 Reduces apoB and Increases apoAI in Other Human and Mouse Hepatoma Cell Lines 
     To ascertain that the regulation of apoB and apoAI by miR-1200 is not specific to Huh-7 cells, its effects in other human hepatoma HepG2 cells were studied. MiR-1200 and anti-1200 decreased and increased media and cellular apoB, respectively ( FIG. 11A ). Further, miR-1200 increased media and cellular apoAI levels by ˜48-54% while anti-1200 had no effect ( FIG. 11B ). These studies showed that miR-1200 regulates apoB and apoAI levels in HepG2 cells. 
     Since mouse models are commonly used to evaluate the role of miRs in lipid metabolism and atherosclerosis, the effects of miR-1200 on apoB and apoAI in mouse hepatoma AML12 cells were examined. Expression of miR-1200 decreased apoB and increased apoAI but had no effect on MTTP and ABCA1 mRNA levels ( FIG. 11C ). Thus, miR-1200 also modulates apoB and apoAI expression in mouse hepatoma cells. 
     Example 5 
     MiR-1200 Reduces LDL and Increases HDL Cholesterol in Western Diet Fed C57BL/6J Mice 
     To investigate the physiological consequences of miR-1200 overexpression, a dose-escalation study in wild type C57BL/6J mice fed a Western diet for 6 weeks was performed ( FIG. 4 ). Mice were first injected with a low dose of miR-1200 (0.1 mg/kg/week) or PBS control. Dosage was increased gradually in the following weeks to 0.3 mg/kg, 0.6 mg/kg and 1 mg/kg per week ( FIG. 4A ). At the end of the study, tissue distribution studies in miR-1200 injected mice showed that liver, spleen and heart contained significant amounts of miR-1200 ( FIG. 4B ). The effects of miR-1200 overexpression in the liver were further investigated. The hepatic accretions of miR-1200 had no effect on the endogenous miR-30c levels ( FIG. 4C ). MiR-1200 significantly reduced hepatic apoB and BCL11B, increased apoAI, and had no effect on MTTP, SR-BI, ABCA1 and ABCG1 mRNA levels ( FIG. 4D ). These studies indicate that miR-1200 accumulated in the liver and reduced the expression of its target genes, but had no effect on non-target genes. 
     Analysis of Plasma Constituents 
     Blood was collected in EDTA containing tubes from overnight fasted mice. Plasma was separated by centrifugation. Total plasma cholesterol, triglyceride, and phospholipid were measured using commercial kits (Thermo Fisher Scientific, Wako Diagnostic). To precipitate apoB-containing lipoproteins, 25 μL of 0.44 mM phosphotungstic acid and 20 mM MgCl 2  were added to 10 μL of plasma, incubated for 5 min at room temperature, and centrifuged at 12,000*g. Supernatants were used to measure cholesterol in HDL. Cholesterol levels in non-HDL fractions were determined by subtracting HDL-cholesterol from total cholesterol. Lipids were extracted from liver homogenates using methanol/chloroform and quantified using kits. Plasma ALT, AST, glucose and CK were measured using commercial available kits (Pointe Scientific, Wako Diagnostic, and Thermo scientific) according to the manufacturer&#39;s instructions. 
     Analyses of plasma constituents revealed no significant changes in total plasma cholesterol ( FIG. 4E ). However, miR-1200 reduced non-HDL (LDL) cholesterol at the lowest 0.1 mg/kg/week dose and the effect persisted at higher doses ( FIG. 4E ). Low dose of miR-1200 had no effect but higher doses of 0.6 and 1 mg/kg/week increased HDL-cholesterol compared with the PBS group ( FIG. 4E ). At low doses, total plasma triglyceride did not change. However, at a 1 mg/kg/week dose, plasma triglycerides were significantly reduced. At all the doses, there were no significant differences in plasma phospholipids, glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) levels in these two groups ( FIG. 4F ). Western blot of plasma proteins showed that miR-1200 reduced apoB48 and apoB100 by 60 and 48%, respectively; increased apoAI by 32%; and had no effect on apoE ( FIG. 4G ). Gel filtration showed that triglyceride in VLDL fractions was decreased, cholesterol and phospholipid were reduced in the LDL fraction, and cholesterol and phospholipid were increased in HDL of the miR-1200 group compared to controls ( FIG. 4H ). These studies showed that miR-1200 reduces non-HDL cholesterol and increases HDL cholesterol without causing liver or muscle toxicity. Thus, miR-1200 differentially modulates plasma lipoproteins with no obvious adverse effects. 
     Example 6 
     MiR-1200 Does Not Cause Hepatosteatosis and Increases Fatty Acid Oxidation (FAO) 
     The effects of miR-1200 on hepatic lipid metabolism were tested. Assimilation of miR-1200 in the liver had no effect on hepatic cholesterol and triglyceride levels, indicating that miR-1200 does not cause hepatic steatosis ( FIG. 5A ). Increased hepatic lipid content is usually observed when apoB-lipoprotein secretion is reduced via MTP inhibition or the use of apoB anti-sense. Previous studies show that miR-30c inhibits hepatic lipoprotein production but does not cause steatosis by reducing lipid synthesis (Soh et al., 2013). 
     The effect of miR-1200 on lipid synthesis and FAO was assessed. In the livers of miR-1200 injected group, FAO was increased by &gt;2-fold but had no effect on the synthesis of different lipids ( FIG. 5B ). Consistent with increases in FAO, these livers had higher expression levels of MCAD, ACOX1, and CPT1 and lower NCOR1 levels, a known repressor of FAO (Fan and Evans, 2015; Mottis et al., 2013) ( FIG. 5C ). Prediction algorithms informed that NCOR1 is a target of miR-1200 ( FIG. 5D ). To test whether miR-1200 regulates FAO by modulating NCOR1 levels, Huh-7 cells were transfected with Scr or miR-1200. Transfection of miR-1200 increased FAO without affecting lipid syntheses ( FIG. 5E ) and reduced NCOR1 mRNA levels ( FIG. 5F ). To determine whether miR-1200 regulates FAO via NCOR1, Huh-7 cells were co-transfected with different combinations of miRs and siRNAs ( FIG. 5G ). MiR-1200 and siNCOR1 significantly increased FAO. siNCOR1+miR-1200 increased FAO to similar extents indicating that miR-1200 and NCOR1 are in the same pathway and that miR-1200 might reduce NCOR1 to increase FAO. Under normal conditions, NCOR1 interacts with PPARα/RXR to reduce the expression of genes involved in FAO. Overexpression of miR-1200 may reduce NCOR1 levels de-repressing the expression of genes involved in FAO ( FIG. 5H ). 
     Fatty acid oxidation and synthesis of fatty acids, triglycerides, and phospholipids: For hepatic FAO, ˜100 mg fresh liver slices were incubated with 0.2 μCi of  14 C-oleate for 2 h. Released  14 C—CO 2  was trapped in phenylethylamine soaked Whatman filter paper and counted (Khatun et al., 2012; Soh et al., 2013). To study FAO in cells, Huh-7 cells were plated in 12-well plates and incubated with DMEM containing 0.4 μCi/ml of  14 C-oleate and covered with phenylethylamine soaked Whatman filter paper for 3 hours at 37° C. At the end of incubation, 200 μl of 1M perchloric acid was added to media and incubated for 1 h at room temperature to precipitate acid-insoluble metabolites, and centrifuged (10 min 12,000*g). The radioactivity in the supernatant and the filter paper was counted. 
     For fatty acid synthesis (de novo lipogenesis), about 50 mg fresh liver slices were incubated with 1 μCi  14 C-acetate. After one hour, the liver slices were washed with PBS and subjected to fatty acids extraction using Petroleum Ether. The radioactivity in fatty acids was measured by scintillation counter. For triglyceride and phospholipid synthesis, 50 mg fresh liver slices were labeled with 1 μCi of  3 H-glycerol for 1 hour. Total lipids were extracted by chloroform and methanol and separated on silica-60 Thin Layer Chromatography. The bands containing triglyceride or phospholipid were scraped off from the plates and counted in a scintillation counter. 
     Example 7 
     MiR-1200 Reduces Hepatic Production of apoB-Containing Lipoproteins and Augments Reverse Cholesterol Transport 
     MiR-1200 significantly reduced plasma LDL cholesterol levels ( FIG. 4E ) and cellular and media apoB ( FIGS. 2A-D ,  FIGS. 11A-11C ). Additionally, miR-1200 increased plasma HDL ( FIG. 4E ). The following example assesses whether (1) miR-1200 reduces hepatic VLDL production to lower plasma LDL and (2) miR-1200 enhances RCT from lipid-loaded macrophages to plasma, liver and feces. Western diet-fed male C57BL/6J mice were injected with 1 mg/kg/week miR-1200 or PBS for two weeks. As before, miR-1200 had no effect on total cholesterol, but decreased total triglyceride levels ( FIG. 6A ). Quantifications of cholesterol in different lipoproteins showed that miR-1200 decreased LDL-cholesterol and increased HDL cholesterol ( FIG. 6A ). After the second weekly injection, mice were divided into two groups and used for VLDL production and RCT. For VLDL production, overnight fasted mice were injected intraperitoneally with poloxamer 407 (1 mg/g body weight) and 150 μCi of [35S]Promix (Soh et al., 2013) to inhibit lipoprotein lipase. Blood was removed at indicated time points. apoB was immunoprecipitated, separated on SDS-PAGE, and visualized by autoradiography. For immunoprecipitation, plasma (100 μl) was incubated for 16 h with 5 μl of anti-apoB polyclonal antibody (Texas Academy Biosciences, Product ID 20A-G1) in NET buffer (50 mM Tris, pH 7.4, 150 mM NaCl, 5 mM EDTA, 0.5% Triton X-100 and 0.1% SDS) and Protein A/G PLUS-Agarose beads (Sigma, sc-2003). 
     MiR-1200 injected mice accumulated reduced amounts of triglyceride in plasma over time ( FIG. 6B ). Triglyceride production rates were 3-fold lower in the miR-1200 group (138 mg·dL −1 ·hour −1 ) compared with the PBS group (432 mg·dL −1 ·hour −1 ). Additionally, the amounts of newly synthesized apoB were significantly reduced in the plasma of miR-1200 group ( FIG. 6C ). These studies indicate that miR-1200 significantly diminishes hepatic production of triglyceride-rich apoB-containing lipoproteins. 
     For in vivo RCT (McGillicuddy et al., 2009), mice were injected with  3 H-cholesterol labeled macrophages. After 48 hours, miR-1200 treated mice had 13% more  3 H-cholesterol in plasma, 22% more in feces, and 16% more in the liver compared with PBS controls ( FIG. 6D ). These studies indicated that miR-1200 enhances RCT from macrophages. 
     For RCT (Rohatgi et al., 2014; Khera et al., 2011; McGillicuddy et al., 2009), J774A.1 cells (10 5 /well) were plated in 6-well plates one day before loading. For loading, cells were incubated with Ac-LDL (50 μg/ml)+ 3 H-cholesterol (5 μCi/ml) in DMEM containing 10% FBS for 48 hours. After washing with PBS three times, cells were incubated with 0.5% BSA containing DMEM for one hour. Cells were harvested, washed, and suspended in 0.5% BSA containing DMEM. A small aliquot of cells was counted in scintillation counter to measure the total injected dpm. 300 μl of cells were injected into each mouse. Samples were collected after 48 hours. 
     Increases in RCT are due to augmentations in cholesterol efflux potential of HDL. Total plasma and HDL isolated from miR-1200 treated mice effluxed ˜26% more radiolabeled cholesterol than controls ( FIG. 6E ). These data showed that HDL levels increased by miR-1200 are efficient in cholesterol efflux. 
     Cholesterol Efflux Assay 
     For cholesterol efflux (Khera et al., 2011), J774A.1 cells (1.2×10 4 ) were plated in each well of a 96-well plate one day before loading. For loading, cells were incubated with DMEM containing 50 μg/mL Ac-LDL, 0.2 μCi/mL  3 H-cholesterol, 10% FBS and 0.5% BSA for 48 hours. Then cells were washed three times with PBS and equilibrated in serum free DMEM containing 2 μM of LXR agonist TO901317 and 0.5% BSA for 24 hours. HDL or whole plasma (5%, v/v) was used as cholesterol acceptor. DMEM containing 0.5% BSA was used as control. The efflux was performed in the presence of TO901317 and 0.5% BSA for 6 hours. After efflux, radiolabeled cholesterol in media and cells were counted separately. Percent Cholesterol efflux=media counts/(media counts+cell counts)*100% −% blank efflux. 
     Example 8 
     MiR-1200 Reduces Atherosclerosis in Apoe −/−  Mice 
     This example demonstrates that miR-1200 can reduce atherosclerosis. Western diet fed Apoe −/−  mice were injected with 1 mg/kg/week miR-1200 for 7 weeks ( FIGS. 12A-12E ). Injection of miR-1200 significantly reduced hepatic apoB, BCL11B, and NCOR1; increased ApoAI, and CPT1; and had no effect on MTTP, ABCA1, and ABCG1 mRNA levels compared with controls ( FIG. 12A ). Lipid analyses revealed no significant differences in hepatic cholesterol and triglyceride in both the groups ( FIG. 12B ). Plasma total cholesterol significantly reduced starting from week 4 ( FIG. 12C ). There were no significant changes in plasma triglyceride, ALT, AST and CK levels ( FIG. 12D ). Oil Red O staining of aortas showed significantly reduced lesion size in the miR-1200 group ( FIG. 12E ). These studies indicated that miR-1200 reduces atherosclerotic plaques. 
     In a second experiment, mice fed a Western diet were injected with 2 mg/kg/week of miR-1200 or PBS for 5 weeks. Again, miR-1200 accumulated in the liver, kidney, spleen and heart of these mice and hepatic accretions had no effect on miR-30c expression ( FIG. 7A ). The mRNA levels of apoB, BCL11B and NCOR1 were significantly reduced, apoAI and CPT1 were increased, and MTTP, SR-B1 and ABCA1 were not changed ( FIG. 7B ). Total cholesterol and phospholipids in plasma were significantly decreased by miR-1200 treatment, while plasma triglyceride levels were unaffected ( FIG. 7C ). FPLC analyses showed that reductions in cholesterol and phospholipids were mainly in apoB-containing lipoproteins ( FIG. 7D ). Again, liver and muscle injury markers (ALT, AST and CK) were not elevated in plasma ( FIG. 7E ). Further, miR-1200 did not cause lipid accumulation in the liver, as hepatic cholesterol and triglyceride were the same as in the control group ( FIG. 7F ). In miR-1200 injected Apoe −/−  mice, aortic arch lesions were significantly reduced ( FIG. 7G ). Further, lipid accumulation in the aortas determined by Oil Red O staining was significantly lower in the miR-1200 group ( FIG. 7H ). Therefore, these studies show that miR-1200 decreases total plasma cholesterol levels and reduces atherosclerosis in Apoe −/−  mice. 
     Example 9 
     Cell Culture 
     Cells used in the foregoing Examples including, Human hepatoma Huh-7 and HepG2; mouse hepatoma AML12; and mouse macrophage J774A.1 cells from American Type Culture Collection were maintained in Dulbecco&#39;s Modified Eagle Medium (DMEM) containing 10% fetal bovine serum, 1% penicillin-streptomycin and 1% L-glutamine in a 37° C., 5% CO2 cell culture incubator. 
     Example 10 
     Methods of Preventing and Treating Hyperlipidemia and Atherosclerosis in Human Patients 
     A therapeutically effective amount of a miR comprising SEQ ID NO:1 is administered to a human patient, wherein LDL is decreased and HDL is increased, without causing liver or muscle injury. The miR is administered at a dose of 0.1-2 mg/kg/week, with the specific dosage chosen based on the type and severity of the disease and patient response and characteristics. A dose as low as 0.1 mg/kg/week, i.e. a dose 10-fold lower than that used in mice, may be therapeutically effective, given the slower metabolic rate in humans. To achieve optimal response, the dose may be increased up to 1 mg/kg/week, the same dose as in mice. If needed, the dose may be further increased up to 2 mg/kg/week. Such dose optimization is within the skill of a person of ordinary skill in the art. 
     Example 11 
     Methods of Increasing apoAI levels by Reducing NRIP1 
     A therapeutically effective amount of an NRIP1 inhibitor is administered to cells in vitro or in vivo, thereby increasing the expression of apoAI. The inhibitor may be a nucleic acid inhibitor, such as an siRNA, e.g. with the sequence of SEQ ID NO:3, shown in Table 4. Alternatively, the NRIP1 inhibitor may be a small molecule or a protein, such as an antibody or a fusion protein. To further enhance apoAI expression, the NRIP1 inhibitor is optionally administered in combination with an inhibitor of BCL11B and/or an inhibitor of apoB expression or activity. When administered to an animal or a human patient, the specific dosage of each inhibitor is chosen and adjusted based on the type and severity of the disease, as well as the patient response and characteristics. 
     REFERENCES 
     
         
         Chiou et al., Journal of Controlled Release. 2012; 159:240-25 
         Cornier, M. A. and Eckel, R. H. (2015). Non-traditional dosing of statins in statin-intolerant patients-is it worth a try? Curr. Atheroscler. Rep. 17, 475. 
         Fisher, E. A. and Ginsberg, H. N. (2002). Complexity in the secretory pathway: the assembly and secretion of apolipoprotein B-containing lipoproteins. J. Biol. Chem. 277, 17377-17380. 
         Khatun, I., Zeissig, S., Iqbal, J., Wang, M., Curiel, D., Shelness, G. S., Blumberg, R. S., and Hussain, M. M. (2012). Phospholipid transfer activity of MTP promotes assembly of phospholipid-rich apoB-containing lipoproteins and reduces plasma as well as hepatic lipids in mice. Hepatology 55, 1356-1368. 
         Khera, A. V., Cuchel, M., de, l.L.-M., Rodrigues, A., Burke, M. F., Jafri, K., French, B. C., Phillips, J. A., Mucksavage, M. L., Wilensky, R. L., Mohler, E. R., Rothblat, G. H., and Rader, D. J. (2011). Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N. Engl. J. Med. 364, 127-135. 
         Liu et al., Molecular Pharmaceutics. 2011; 8:250-259 
         McGillicuddy, F. C., de la Llera, M. M., Hinkle, C. C., Joshi, M. R., Chiquoine, E. H., Billheimer, J. T., Rothblat, G. H., and Reilly, M. P. (2009). Inflammation impairs reverse cholesterol transport in vivo. Circulation 119, 1135-1145. 
         Medina et al., Curr Pharm Des. 2004; 10(24):2981-9 
         Rohatgi, A., Khera, A., Berry, J. D., Givens, E. G., Ayers, C. R., Wedin, K. E., Neeland, I. J., Yuhanna, I. S., Rader, D. R., De Lemos, J. A., and Shaul, P. W. (2014). HDL cholesterol efflux capacity and incident cardiovascular events. N. Engl. J. Med. 371, 2383-2393. 
         Soh, J., Iqbal, J., Queiroz, J., Fernandez-Hernando, C., and Hussain, M. M. (2013). MicroRNA-30c reduces hyperlipidemia and atherosclesrosis by decreasing lipid synthesis and lipoprotein secretion. Nat. Med. 19, 892-900. 
         Walsh, M. T., Iqbal, J., Josekutty, J., Soh, J., Di, L. E., Ozaydin, E., Gunduz, M., Tarugi, P., and Hussain, M. M. (2015). Novel Abetalipoproteinemia Missense Mutation Highlights the Importance of the N-Terminal beta-Barrel in Microsomal Triglyceride Transfer Protein Function. Circ. Cardiovasc. Genet. 8, 677-687. 
         Zhang et al., J Control Release. 2013, 172(3):962-74. 
       
    
     
       
         
           
               
             
               
                 APPENDIX A 
               
               
                   
               
             
            
               
                   HOMO SAPIENS  APOLIPOPROTEIN B (APOB), MRNA 
               
               
                 (GENE ACCESSION NM_000384) 
               
            
           
           
               
               
            
               
                 1 
                 ATTCCCACCG GGACCTGCGG GGCTGAGTGC CCTTCTCGGT TGCTGCCGCT GAGGAGCCCG 
               
               
                   
               
               
                 61 
                 CCCAGCCAGC CAGGGCCGCG AGGCCGAGGC CAGGCCGCAG CCCAGGAGCC GCCCCACCGC 
               
               
                   
               
               
                 121 
                 AGCTGGCGAT GGACCCGCCG AGGCCCGCGC TGCTGGCGCT GCTGGCGCTG CCTGCGCTGC 
               
               
                   
               
               
                 181 
                 TGCTGCTGCT GCTGGCGGGC GCCAGGGCCG AAGAGGAAAT GCTGGAAAAT GTCAGCCTGG 
               
               
                   
               
               
                 241 
                 TCTGTCCAAA AGATGCGACC CGATTCAAGC ACCTCCGGAA GTACACATAC AACTATGAGG 
               
               
                   
               
               
                 301 
                 CTGAGAGTTC CAGTGGAGTC CCTGGGACTG CTGATTCAAG AAGTGCCACC AGGATCAACT 
               
               
                   
               
               
                 361 
                 GCAAGGTTGA GCTGGAGGTT CCCCAGCTCT GCAGCTTCAT CCTGAAGACC AGCCAGTGCA 
               
               
                   
               
               
                 421 
                 CCCTGAAAGA GGTGTATGGC TTCAACCCTG AGGGCAAAGC CTTGCTGAAG AAAACCAAGA 
               
               
                   
               
               
                 481 
                 ACTCTGAGGA GTTTGCTGCA GCCATGTCCA GGTATGAGCT CAAGCTGGCC ATTCCAGAAG 
               
               
                   
               
               
                 541 
                 GGAAGCAGGT TTTCCTTTAC CCGGAGAAAG ATGAACCTAC TTACATCCTG AACATCAAGA 
               
               
                   
               
               
                 601 
                 GGGGCATCAT TTCTGCCCTC CTGGTTCCCC CAGAGACAGA AGAAGCCAAG CAAGTGTTGT 
               
               
                   
               
               
                 661 
                 TTCTGGATAC CGTGTATGGA AACTGCTCCA CTCACTTTAC CGTCAAGACG AGGAAGGGCA 
               
               
                   
               
               
                 721 
                 ATGTGGCAAC AGAAATATCC ACTGAAAGAG ACCTGGGGCA GTGTGATCGC TTCAAGCCCA 
               
               
                   
               
               
                 781 
                 TCCGCACAGG CATCAGCCCA CTTGCTCTCA TCAAAGGCAT GACCCGCCCC TTGTCAACTC 
               
               
                   
               
               
                 841 
                 TGATCAGCAG CAGCCAGTCC TGTCAGTACA CACTGGACGC TAAGAGGAAG CATGTGGCAG 
               
               
                   
               
               
                 901 
                 AAGCCATCTG CAAGGAGCAA CACCTCTTCC TGCCTTTCTC CTACAAGAAT AAGTATGGGA 
               
               
                   
               
               
                 961 
                 TGGTAGCACA AGTGACACAG ACTTTGAAAC TTGAAGACAC ACCAAAGATC AACAGCCGCT 
               
               
                   
               
               
                 1021 
                 TCTTTGGTGA AGGTACTAAG AAGATGGGCC TCGCATTTGA GAGCACCAAA TCCACATCAC 
               
               
                   
               
               
                 1081 
                 CTCCAAAGCA GGCCGAAGCT GTTTTGAAGA CTCTCCAGGA ACTGAAAAAA CTAACCATCT 
               
               
                   
               
               
                 1141 
                 CTGAGCAAAA TATCCAGAGA GCTAATCTCT TCAATAAGCT GGTTACTGAG CTGAGAGGCC 
               
               
                   
               
               
                 1201 
                 TCAGTGATGA AGCAGTCACA TCTCTCTTGC CACAGCTGAT TGAGGTGTCC AGCCCCATCA 
               
               
                   
               
               
                 1261 
                 CTTTACAAGC CTTGGTTCAG TGTGGACAGC CTCAGTGCTC CACTCACATC CTCCAGTGGC 
               
               
                   
               
               
                 1321 
                 TGAAACGTGT GCATGCCAAC CCCCTTCTGA TAGATGTGGT CACCTACCTG GTGGCCCTGA 
               
               
                   
               
               
                 1381 
                 TCCCCGAGCC CTCAGCACAG CAGCTGCGAG AGATCTTCAA CATGGCGAGG GATCAGCGCA 
               
               
                   
               
               
                 1441 
                 GCCGAGCCAC CTTGTATGCG CTGAGCCACG CGGTCAACAA CTATCATAAG ACAAACCCTA 
               
               
                   
               
               
                 1501 
                 CAGGGACCCA GGAGCTGCTG GACATTGCTA ATTACCTGAT GGAACAGATT CAAGATGACT 
               
               
                   
               
               
                 1561 
                 GCACTGGGGA TGAAGATTAC ACCTATTTGA TTCTGCGGGT CATTGGAAAT ATGGGCCAAA 
               
               
                   
               
               
                 1621 
                 CCATGGAGCA GTTAACTCCA GAACTCAAGT CTTCAATCCT GAAATGTGTC CAAAGTACAA 
               
               
                   
               
               
                 1681 
                 AGCCATCACT GATGATCCAG AAAGCTGCCA TCCAGGCTCT GCGGAAAATG GAGCCTAAAG 
               
               
                   
               
               
                 1741 
                 ACAAGGACCA GGAGGTTCTT CTTCAGACTT TCCTTGATGA TGCTTCTCCG GGAGATAAGC 
               
               
                   
               
               
                 1801 
                 GACTGGCTGC CTATCTTATG TTGATGAGGA GTCCTTCACA GGCAGATATT AACAAAATTG 
               
               
                   
               
               
                 1861 
                 TCCAAATTCT ACCATGGGAA CAGAATGAGC AAGTGAAGAA CTTTGTGGCT TCCCATATTG 
               
               
                   
               
               
                 1921 
                 CCAATATCTT GAACTCAGAA GAATTGGATA TCCAAGATCT GAAAAAGTTA GTGAAAGAAG 
               
               
                   
               
               
                 1981 
                 CTCTGAAAGA ATCTCAACTT CCAACTGTCA TGGACTTCAG AAAATTCTCT CGGAACTATC 
               
               
                   
               
               
                 2041 
                 AACTCTACAA ATCTGTTTCT CTTCCATCAC TTGACCCAGC CTCAGCCAAA ATAGAAGGGA 
               
               
                   
               
               
                 2101 
                 ATCTTATATT TGATCCAAAT AACTACCTTC CTAAAGAAAG CATGCTGAAA ACTACCCTCA 
               
               
                   
               
               
                 2161 
                 CTGCCTTTGG ATTTGCTTCA GCTGACCTCA TCGAGATTGG CTTGGAAGGA AAAGGCTTTG 
               
               
                   
               
               
                 2221 
                 AGCCAACATT GGAAGCTCTT TTTGGGAAGC AAGGATTTTT CCCAGACAGT GTCAACAAAG 
               
               
                   
               
               
                 2281 
                 CTTTGTACTG GGTTAATGGT CAAGTTCCTG ATGGTGTCTC TAAGGTCTTA GTGGACCACT 
               
               
                   
               
               
                 2341 
                 TTGGCTATAC CAAAGATGAT AAACATGAGC AGGATATGGT AAATGGAATA ATGCTCAGTG 
               
               
                   
               
               
                 2401 
                 TTGAGAAGCT GATTAAAGAT TTGAAATCCA AAGAAGTCCC GGAAGCCAGA GCCTACCTCC 
               
               
                   
               
               
                 2461 
                 GCATCTTGGG AGAGGAGCTT GGTTTTGCCA GTCTCCATGA CCTCCAGCTC CTGGGAAAGC 
               
               
                   
               
               
                 2521 
                 TGCTTCTGAT GGGTGCCCGC ACTCTGCAGG GGATCCCCCA GATGATTGGA GAGGTCATCA 
               
               
                   
               
               
                 2581 
                 GGAAGGGCTC AAAGAATGAC TTTTTTCTTC ACTACATCTT CATGGAGAAT GCCTTTGAAC 
               
               
                   
               
               
                 2641 
                 TCCCCACTGG AGCTGGATTA CAGTTGCAAA TATCTTCATC TGGAGTCATT GCTCCCGGAG 
               
               
                   
               
               
                 2701 
                 CCAAGGCTGG AGTAAAACTG GAAGTAGCCA ACATGCAGGC TGAACTGGTG GCAAAACCCT 
               
               
                   
               
               
                 2761 
                 CCGTGTCTGT GGAGTTTGTG ACAAATATGG GCATCATCAT TCCGGACTTC GCTAGGAGTG 
               
               
                   
               
               
                 2821 
                 GGGTCCAGAT GAACACCAAC TTCTTCCACG AGTCGGGTCT GGAGGCTCAT GTTGCCCTAA 
               
               
                   
               
               
                 2881 
                 AAGCTGGGAA GCTGAAGTTT ATCATTCCTT CCCCAAAGAG ACCAGTCAAG CTGCTCAGTG 
               
               
                   
               
               
                 2941 
                 GAGGCAACAC ATTACATTTG GTCTCTACCA CCAAAACGGA GGTGATCCCA CCTCTCATTG 
               
               
                   
               
               
                 3001 
                 AGAACAGGCA GTCCTGGTCA GTTTGCAAGC AAGTCTTTCC TGGCCTGAAT TACTGCACCT 
               
               
                   
               
               
                 3061 
                 CAGGCGCTTA CTCCAACGCC AGCTCCACAG ACTCCGCCTC CTACTATCCG CTGACCGGGG 
               
               
                   
               
               
                 3121 
                 ACACCAGATT AGAGCTGGAA CTGAGGCCTA CAGGAGAGAT TGAGCAGTAT TCTGTCAGCG 
               
               
                   
               
               
                 3181 
                 CAACCTATGA GCTCCAGAGA GAGGACAGAG CCTTGGTGGA TACCCTGAAG TTTGTAACTC 
               
               
                   
               
               
                 3241 
                 AAGCAGAAGG TGCGAAGCAG ACTGAGGCTA CCATGACATT CAAATATAAT CGGCAGAGTA 
               
               
                   
               
               
                 3301 
                 TGACCTTGTC CAGTGAAGTC CAAATTCCGG ATTTTGATGT TGACCTCGGA ACAATCCTCA 
               
               
                   
               
               
                 3361 
                 GAGTTAATGA TGAATCTACT GAGGGCAAAA CGTCTTACAG ACTCACCCTG GACATTCAGA 
               
               
                   
               
               
                 3421 
                 ACAAGAAAAT TACTGAGGTC GCCCTCATGG GCCACCTAAG TTGTGACACA AAGGAAGAAA 
               
               
                   
               
               
                 3481 
                 GAAAAATCAA GGGTGTTATT TCCATACCCC GTTTGCAAGC AGAAGCCAGA AGTGAGATCC 
               
               
                   
               
               
                 3541 
                 TCGCCCACTG GTCGCCTGCC AAACTGCTTC TCCAAATGGA CTCATCTGCT ACAGCTTATG 
               
               
                   
               
               
                 3601 
                 GCTCCACAGT TTCCAAGAGG GTGGCATGGC ATTATGATGA AGAGAAGATT GAATTTGAAT 
               
               
                   
               
               
                 3661 
                 GGAACACAGG CACCAATGTA GATACCAAAA AAATGACTTC CAATTTCCCT GTGGATCTCT 
               
               
                   
               
               
                 3721 
                 CCGATTATCC TAAGAGCTTG CATATGTATG CTAATAGACT CCTGGATCAC AGAGTCCCTC 
               
               
                   
               
               
                 3781 
                 AAACAGACAT GACTTTCCGG CACGTGGGTT CCAAATTAAT AGTTGCAATG AGCTCATGGC 
               
               
                   
               
               
                 3841 
                 TTCAGAAGGC ATCTGGGAGT CTTCCTTATA CCCAGACTTT GCAAGACCAC CTCAATAGCC 
               
               
                   
               
               
                 3901 
                 TGAAGGAGTT CAACCTCCAG AACATGGGAT TGCCAGACTT CCACATCCCA GAAAACCTCT 
               
               
                   
               
               
                 3961 
                 TCTTAAAAAG CGATGGCCGG GTCAAATATA CCTTGAACAA GAACAGTTTG AAAATTGAGA 
               
               
                   
               
               
                 4021 
                 TTCCTTTGCC TTTTGGTGGC AAATCCTCCA GAGATCTAAA GATGTTAGAG ACTGTTAGGA 
               
               
                   
               
               
                 4081 
                 CACCAGCCCT CCACTTCAAG TCTGTGGGAT TCCATCTGCC ATCTCGAGAG TTCCAAGTCC 
               
               
                   
               
               
                 4141 
                 CTACTTTTAC CATTCCCAAG TTGTATCAAC TGCAAGTGCC TCTCCTGGGT GTTCTAGACC 
               
               
                   
               
               
                 4201 
                 TCTCCACGAA TGTCTACAGC AACTTGTACA ACTGGTCCGC CTCCTACAGT GGTGGCAACA 
               
               
                   
               
               
                 4261 
                 CCAGCACAGA CCATTTCAGC CTTCGGGCTC GTTACCACAT GAAGGCTGAC TCTGTGGTTG 
               
               
                   
               
               
                 4321 
                 ACCTGCTTTC CTACAATGTG CAAGGATCTG GAGAAACAAC ATATGACCAC AAGAATACGT 
               
               
                   
               
               
                 4381 
                 TCACACTATC ATGTGATGGG TCTCTACGCC ACAAATTTCT AGATTCGAAT ATCAAATTCA 
               
               
                   
               
               
                 4441 
                 GTCATGTAGA AAAACTTGGA AACAACCCAG TCTCAAAAGG TTTACTAATA TTCGATGCAT 
               
               
                   
               
               
                 4501 
                 CTAGTTCCTG GGGACCACAG ATGTCTGCTT CAGTTCATTT GGACTCCAAA AAGAAACAGC 
               
               
                   
               
               
                 4561 
                 ATTTGTTTGT CAAAGAAGTC AAGATTGATG GGCAGTTCAG AGTCTCTTCG TTCTATGCTA 
               
               
                   
               
               
                 4621 
                 AAGGCACATA TGGCCTGTCT TGTCAGAGGG ATCCTAACAC TGGCCGGCTC AATGGAGAGT 
               
               
                   
               
               
                 4681 
                 CCAACCTGAG GTTTAACTCC TCCTACCTCC AAGGCACCAA CCAGATAACA GGAAGATATG 
               
               
                   
               
               
                 4741 
                 AAGATGGAAC CCTCTCCCTC ACCTCCACCT CTGATCTGCA AAGTGGCATC ATTAAAAATA 
               
               
                   
               
               
                 4801 
                 CTGCTTCCCT AAAGTATGAG AACTACGAGC TGACTTTAAA ATCTGACACC AATGGGAAGT 
               
               
                   
               
               
                 4861 
                 ATAAGAACTT TGCCACTTCT AACAAGATGG ATATGACCTT CTCTAAGCAA AATGCACTGC 
               
               
                   
               
               
                 4921 
                 TGCGTTCTGA ATATCAGGCT GATTACGAGT CATTGAGGTT CTTCAGCCTG CTTTCTGGAT 
               
               
                   
               
               
                 4981 
                 CACTAAATTC CCATGGTCTT GAGTTAAATG CTGACATCTT AGGCACTGAC AAAATTAATA 
               
               
                   
               
               
                 5041 
                 GTGGTGCTCA CAAGGCGACA CTAAGGATTG GCCAAGATGG AATATCTACC AGTGCAACGA 
               
               
                   
               
               
                 5101 
                 CCAACTTGAA GTGTAGTCTC CTGGTGCTGG AGAATGAGCT GAATGCAGAG CTTGGCCTCT 
               
               
                   
               
               
                 5161 
                 CTGGGGCATC TATGAAATTA ACAACAAATG GCCGCTTCAG GGAACACAAT GCAAAATTCA 
               
               
                   
               
               
                 5221 
                 GTCTGGATGG GAAAGCCGCC CTCACAGAGC TATCACTGGG AAGTGCTTAT CAGGCCATGA 
               
               
                   
               
               
                 5281 
                 TTCTGGGTGT CGACAGCAAA AACATTTTCA ACTTCAAGGT CAGTCAAGAA GGACTTAAGC 
               
               
                   
               
               
                 5341 
                 TCTCAAATGA CATGATGGGC TCATATGCTG AAATGAAATT TGACCACACA AACAGTCTGA 
               
               
                   
               
               
                 5401 
                 ACATTGCAGG CTTATCACTG GACTTCTCTT CAAAACTTGA CAACATTTAC AGCTCTGACA 
               
               
                   
               
               
                 5461 
                 AGTTTTATAA GCAAACTGTT AATTTACAGC TACAGCCCTA TTCTCTGGTA ACTACTTTAA 
               
               
                   
               
               
                 5521 
                 ACAGTGACCT GAAATACAAT GCTCTGGATC TCACCAACAA TGGGAAACTA CGGCTAGAAC 
               
               
                   
               
               
                 5581 
                 CCCTGAAGCT GCATGTGGCT GGTAACCTAA AAGGAGCCTA CCAAAATAAT GAAATAAAAC 
               
               
                   
               
               
                 5641 
                 ACATCTATGC CATCTCTTCT GCTGCCTTAT CAGCAAGCTA TAAAGCAGAC ACTGTTGCTA 
               
               
                   
               
               
                 5701 
                 AGGTTCAGGG TGTGGAGTTT AGCCATCGGC TCAACACAGA CATCGCTGGG CTGGCTTCAG 
               
               
                   
               
               
                 5761 
                 CCATTGACAT GAGCACAAAC TATAATTCAG ACTCACTGCA TTTCAGCAAT GTCTTCCGTT 
               
               
                   
               
               
                 5821 
                 CTGTAATGGC CCCGTTTACC ATGACCATCG ATGCACATAC AAATGGCAAT GGGAAACTCG 
               
               
                   
               
               
                 5881 
                 CTCTCTGGGG AGAACATACT GGGCAGCTGT ATAGCAAATT CCTGTTGAAA GCAGAACCTC 
               
               
                   
               
               
                 5941 
                 TGGCATTTAC TTTCTCTCAT GATTACAAAG GCTCCACAAG TCATCATCTC GTGTCTAGGA 
               
               
                   
               
               
                 6001 
                 AAAGCATCAG TGCAGCTCTT GAACACAAAG TCAGTGCCCT GCTTACTCCA GCTGAGCAGA 
               
               
                   
               
               
                 6061 
                 CAGGCACCTG GAAACTCAAG ACCCAATTTA ACAACAATGA ATACAGCCAG GACTTGGATG 
               
               
                   
               
               
                 6121 
                 CTTACAACAC TAAAGATAAA ATTGGCGTGG AGCTTACTGG ACGAACTCTG GCTGACCTAA 
               
               
                   
               
               
                 6181 
                 CTCTACTAGA CTCCCCAATT AAAGTGCCAC TTTTACTCAG TGAGCCCATC AATATCATTG 
               
               
                   
               
               
                 6241 
                 ATGCTTTAGA GATGAGAGAT GCCGTTGAGA AGCCCCAAGA ATTTACAATT GTTGCTTTTG 
               
               
                   
               
               
                 6301 
                 TAAAGTATGA TAAAAACCAA GATGTTCACT CCATTAACCT CCCATTTTTT GAGACCTTGC 
               
               
                   
               
               
                 6361 
                 AAGAATATTT TGAGAGGAAT CGACAAACCA TTATAGTTGT ACTGGAAAAC GTACAGAGAA 
               
               
                   
               
               
                 6421 
                 ACCTGAAGCA CATCAATATT GATCAATTTG TAAGAAAATA CAGAGCAGCC CTGGGAAAAC 
               
               
                   
               
               
                 6481 
                 TCCCACAGCA AGCTAATGAT TATCTGAATT CATTCAATTG GGAGAGACAA GTTTCACATG 
               
               
                   
               
               
                 6541 
                 CCAAGGAGAA ACTGACTGCT CTCACAAAAA AGTATAGAAT TACAGAAAAT GATATACAAA 
               
               
                   
               
               
                 6601 
                 TTGCATTAGA TGATGCCAAA ATCAACTTTA ATGAAAAACT ATCTCAACTG CAGACATATA 
               
               
                   
               
               
                 6661 
                 TGATACAATT TGATCAGTAT ATTAAAGATA GTTATGATTT ACATGATTTG AAAATAGCTA 
               
               
                   
               
               
                 6721 
                 TTGCTAATAT TATTGATGAA ATCATTGAAA AATTAAAAAG TCTTGATGAG CACTATCATA 
               
               
                   
               
               
                 6781 
                 TCCGTGTAAA TTTAGTAAAA ACAATCCATG ATCTACATTT GTTTATTGAA AATATTGATT 
               
               
                   
               
               
                 6841 
                 TTAACAAAAG TGGAAGTAGT ACTGCATCCT GGATTCAAAA TGTGGATACT AAGTACCAAA 
               
               
                   
               
               
                 6901 
                 TCAGAATCCA GATACAAGAA AAACTGCAGC AGCTTAAGAG ACACATACAG AATATAGACA 
               
               
                   
               
               
                 6961 
                 TCCAGCACCT AGCTGGAAAG TTAAAACAAC ACATTGAGGC TATTGATGTT AGAGTGCTTT 
               
               
                   
               
               
                 7021 
                 TAGATCAATT GGGAACTACA ATTTCATTTG AAAGAATAAA TGACGTTCTT GAGCATGTCA 
               
               
                   
               
               
                 7081 
                 AACACTTTGT TATAAATCTT ATTGGGGATT TTGAAGTAGC TGAGAAAATC AATGCCTTCA 
               
               
                   
               
               
                 7141 
                 GAGCCAAAGT CCATGAGTTA ATCGAGAGGT ATGAAGTAGA CCAACAAATC CAGGTTTTAA 
               
               
                   
               
               
                 7201 
                 TGGATAAATT AGTAGAGTTG GCCCACCAAT ACAAGTTGAA GGAGACTATT CAGAAGCTAA 
               
               
                   
               
               
                 7261 
                 GCAATGTCCT ACAACAAGTT AAGATAAAAG ATTACTTTGA GAAATTGGTT GGATTTATTG 
               
               
                   
               
               
                 7321 
                 ATGATGCTGT CAAGAAGCTT AATGAATTAT CTTTTAAAAC ATTCATTGAA GATGTTAACA 
               
               
                   
               
               
                 7381 
                 AATTCCTTGA CATGTTGATA AAGAAATTAA AGTCATTTGA TTACCACCAG TTTGTAGATG 
               
               
                   
               
               
                 7441 
                 AAACCAATGA CAAAATCCGT GAGGTGACTC AGAGACTCAA TGGTGAAATT CAGGCTCTGG 
               
               
                   
               
               
                 7501 
                 AACTACCACA AAAAGCTGAA GCATTAAAAC TGTTTTTAGA GGAAACCAAG GCCACAGTTG 
               
               
                   
               
               
                 7561 
                 CAGTGTATCT GGAAAGCCTA CAGGACACCA AAATAACCTT AATCATCAAT TGGTTACAGG 
               
               
                   
               
               
                 7621 
                 AGGCTTTAAG TTCAGCATCT TTGGCTCACA TGAAGGCCAA ATTCCGAGAG ACCCTAGAAG 
               
               
                   
               
               
                 7681 
                 ATACACGAGA CCGAATGTAT CAAATGGACA TTCAGCAGGA ACTTCAACGA TACCTGTCTC 
               
               
                   
               
               
                 7741 
                 TGGTAGGCCA GGTTTATAGC ACACTTGTCA CCTACATTTC TGATTGGTGG ACTCTTGCTG 
               
               
                   
               
               
                 7801 
                 CTAAGAACCT TACTGACTTT GCAGAGCAAT ATTCTATCCA AGATTGGGCT AAACGTATGA 
               
               
                   
               
               
                 7861 
                 AAGCATTGGT AGAGCAAGGG TTCACTGTTC CTGAAATCAA GACCATCCTT GGGACCATGC 
               
               
                   
               
               
                 7921 
                 CTGCCTTTGA AGTCAGTCTT CAGGCTCTTC AGAAAGCTAC CTTCCAGACA CCTGATTTTA 
               
               
                   
               
               
                 7981 
                 TAGTCCCCCT AACAGATTTG AGGATTCCAT CAGTTCAGAT AAACTTCAAA GACTTAAAAA 
               
               
                   
               
               
                 8041 
                 ATATAAAAAT CCCATCCAGG TTTTCCACAC CAGAATTTAC CATCCTTAAC ACCTTCCACA 
               
               
                   
               
               
                 8101 
                 TTCCTTCCTT TACAATTGAC TTTGTAGAAA TGAAAGTAAA GATCATCAGA ACCATTGACC 
               
               
                   
               
               
                 8161 
                 AGATGCTGAA CAGTGAGCTG CAGTGGCCCG TTCCAGATAT ATATCTCAGG GATCTGAAGG 
               
               
                   
               
               
                 8221 
                 TGGAGGACAT TCCTCTAGCG AGAATCACCC TGCCAGACTT CCGTTTACCA GAAATCGCAA 
               
               
                   
               
               
                 8281 
                 TTCCAGAATT CATAATCCCA ACTCTCAACC TTAATGATTT TCAAGTTCCT GACCTTCACA 
               
               
                   
               
               
                 8341 
                 TACCAGAATT CCAGCTTCCC CACATCTCAC ACACAATTGA AGTACCTACT TTTGGCAAGC 
               
               
                   
               
               
                 8401 
                 TATACAGTAT TCTGAAAATC CAATCTCCTC TTTTCACATT AGATGCAAAT GCTGACATAG 
               
               
                   
               
               
                 8461 
                 GGAATGGAAC CACCTCAGCA AACGAAGCAG GTATCGCAGC TTCCATCACT GCCAAAGGAG 
               
               
                   
               
               
                 8521 
                 AGTCCAAATT AGAAGTTCTC AATTTTGATT TTCAAGCAAA TGCACAACTC TCAAACCCTA 
               
               
                   
               
               
                 8581 
                 AGATTAATCC GCTGGCTCTG AAGGAGTCAG TGAAGTTCTC CAGCAAGTAC CTGAGAACGG 
               
               
                   
               
               
                 8641 
                 AGCATGGGAG TGAAATGCTG TTTTTTGGAA ATGCTATTGA GGGAAAATCA AACACAGTGG 
               
               
                   
               
               
                 8701 
                 CAAGTTTACA CACAGAAAAA AATACACTGG AGCTTAGTAA TGGAGTGATT GTCAAGATAA 
               
               
                   
               
               
                 8761 
                 ACAATCAGCT TACCCTGGAT AGCAACACTA AATACTTCCA CAAATTGAAC ATCCCCAAAC 
               
               
                   
               
               
                 8821 
                 TGGACTTCTC TAGTCAGGCT GACCTGCGCA ACGAGATCAA GACACTGTTG AAAGCTGGCC 
               
               
                   
               
               
                 8881 
                 ACATAGCATG GACTTCTTCT GGAAAAGGGT CATGGAAATG GGCCTGCCCC AGATTCTCAG 
               
               
                   
               
               
                 8941 
                 ATGAGGGAAC ACATGAATCA CAAATTAGTT TCACCATAGA AGGACCCCTC ACTTCCTTTG 
               
               
                   
               
               
                 9001 
                 GACTGTCCAA TAAGATCAAT AGCAAACACC TAAGAGTAAA CCAAAACTTG GTTTATGAAT 
               
               
                   
               
               
                 9061 
                 CTGGCTCCCT CAACTTTTCT AAACTTGAAA TTCAATCACA AGTCGATTCC CAGCATGTGG 
               
               
                   
               
               
                 9121 
                 GCCACAGTGT TCTAACTGCT AAAGGCATGG CACTGTTTGG AGAAGGGAAG GCAGAGTTTA 
               
               
                   
               
               
                 9181 
                 CTGGGAGGCA TGATGCTCAT TTAAATGGAA AGGTTATTGG AACTTTGAAA AATTCTCTTT 
               
               
                   
               
               
                 9241 
                 TCTTTTCAGC CCAGCCATTT GAGATCACGG CATCCACAAA CAATGAAGGG AATTTGAAAG 
               
               
                   
               
               
                 9301 
                 TTCGTTTTCC ATTAAGGTTA ACAGGGAAGA TAGACTTCCT GAATAACTAT GCACTGTTTC 
               
               
                   
               
               
                 9361 
                 TGAGTCCCAG TGCCCAGCAA GCAAGTTGGC AAGTAAGTGC TAGGTTCAAT CAGTATAAGT 
               
               
                   
               
               
                 9421 
                 ACAACCAAAA TTTCTCTGCT GGAAACAACG AGAACATTAT GGAGGCCCAT GTAGGAATAA 
               
               
                   
               
               
                 9481 
                 ATGGAGAAGC AAATCTGGAT TTCTTAAACA TTCCTTTAAC AATTCCTGAA ATGCGTCTAC 
               
               
                   
               
               
                 9541 
                 CTTACACAAT AATCACAACT CCTCCACTGA AAGATTTCTC TCTATGGGAA AAAACAGGCT 
               
               
                   
               
               
                 9601 
                 TGAAGGAATT CTTGAAAACG ACAAAGCAAT CATTTGATTT AAGTGTAAAA GCTCAGTATA 
               
               
                   
               
               
                 9661 
                 AGAAAAACAA ACACAGGCAT TCCATCACAA ATCCTTTGGC TGTGCTTTGT GAGTTTATCA 
               
               
                   
               
               
                 9721 
                 GTCAGAGCAT CAAATCCTTT GACAGGCATT TTGAAAAAAA CAGAAACAAT GCATTAGATT 
               
               
                   
               
               
                 9781 
                 TTGTCACCAA ATCCTATAAT GAAACAAAAA TTAAGTTTGA TAAGTACAAA GCTGAAAAAT 
               
               
                   
               
               
                 9841 
                 CTCACGACGA GCTCCCCAGG ACCTTTCAAA TTCCTGGATA CACTGTTCCA GTTGTCAATG 
               
               
                   
               
               
                 9901 
                 TTGAAGTGTC TCCATTCACC ATAGAGATGT CGGCATTCGG CTATGTGTTC CCAAAAGCAG 
               
               
                   
               
               
                 9961 
                 TCAGCATGCC TAGTTTCTCC ATCCTAGGTT CTGACGTCCG TGTGCCTTCA TACACATTAA 
               
               
                   
               
               
                 10021 
                 TCCTGCCATC ATTAGAGCTG CCAGTCCTTC ATGTCCCTAG AAATCTCAAG CTTTCTCTTC 
               
               
                   
               
               
                 10081 
                 CAGATTTCAA GGAATTGTGT ACCATAAGCC ATATTTTTAT TCCTGCCATG GGCAATATTA 
               
               
                   
               
               
                 10141 
                 CCTATGATTT CTCCTTTAAA TCAAGTGTCA TCACACTGAA TACCAATGCT GAACTTTTTA 
               
               
                   
               
               
                 10201 
                 ACCAGTCAGA TATTGTTGCT CATCTCCTTT CTTCATCTTC ATCTGTCATT GATGCACTGC 
               
               
                   
               
               
                 10261 
                 AGTACAAATT AGAGGGCACC ACAAGATTGA CAAGAAAAAG GGGATTGAAG TTAGCCACAG 
               
               
                   
               
               
                 10321 
                 CTCTGTCTCT GAGCAACAAA TTTGTGGAGG GTAGTCATAA CAGTACTGTG AGCTTAACCA 
               
               
                   
               
               
                 10381 
                 CGAAAAATAT GGAAGTGTCA GTGGCAACAA CCACAAAAGC CCAAATTCCA ATTTTGAGAA 
               
               
                   
               
               
                 10441 
                 TGAATTTCAA GCAAGAACTT AATGGAAATA CCAAGTCAAA ACCTACTGTC TCTTCCTCCA 
               
               
                   
               
               
                 10501 
                 TGGAATTTAA GTATGATTTC AATTCTTCAA TGCTGTACTC TACCGCTAAA GGAGCAGTTG 
               
               
                   
               
               
                 10561 
                 ACCACAAGCT TAGCTTGGAA AGCCTCACCT CTTACTTTTC CATTGAGTCA TCTACCAAAG 
               
               
                   
               
               
                 10621 
                 GAGATGTCAA GGGTTCGGTT CTTTCTCGGG AATATTCAGG AACTATTGCT AGTGAGGCCA 
               
               
                   
               
               
                 10681 
                 ACACTTACTT GAATTCCAAG AGCACACGGT CTTCAGTGAA GCTGCAGGGC ACTTCCAAAA 
               
               
                   
               
               
                 10741 
                 TTGATGATAT CTGGAACCTT GAAGTAAAAG AAAATTTTGC TGGAGAAGCC ACACTCCAAC 
               
               
                   
               
               
                 10801 
                 GCATATATTC CCTCTGGGAG CACAGTACGA AAAACCACTT ACAGCTAGAG GGCCTCTTTT 
               
               
                   
               
               
                 10861 
                 TCACCAACGG AGAACATACA AGCAAAGCCA CCCTGGAACT CTCTCCATGG CAAATGTCAG 
               
               
                   
               
               
                 10921 
                 CTCTTGTTCA GGTCCATGCA AGTCAGCCCA GTTCCTTCCA TGATTTCCCT GACCTTGGCC 
               
               
                   
               
               
                 10981 
                 AGGAAGTGGC CCTGAATGCT AACACTAAGA ACCAGAAGAT CAGATGGAAA AATGAAGTCC 
               
               
                   
               
               
                 11041 
                 GGATTCATTC TGGGTCTTTC CAGAGCCAGG TCGAGCTTTC CAATGACCAA GAAAAGGCAC 
               
               
                   
               
               
                 11101 
                 ACCTTGACAT TGCAGGATCC TTAGAAGGAC ACCTAAGGTT CCTCAAAAAT ATCATCCTAC 
               
               
                   
               
               
                 11161 
                 CAGTCTATGA CAAGAGCTTA TGGGATTTCC TAAAGCTGGA TGTAACCACC AGCATTGGTA 
               
               
                   
               
               
                 11221 
                 GGAGACAGCA TCTTCGTGTT TCAACTGCCT TTGTGTACAC CAAAAACCCC AATGGCTATT 
               
               
                   
               
               
                 11281 
                 CATTCTCCAT CCCTGTAAAA GTTTTGGCTG ATAAATTCAT TATTCCTGGG CTGAAACTAA 
               
               
                   
               
               
                 11341 
                 ATGATCTAAA TTCAGTTCTT GTCATGCCTA CGTTCCATGT CCCATTTACA GATCTTCAGG 
               
               
                   
               
               
                 11401 
                 TTCCATCGTG CAAACTTGAC TTCAGAGAAA TACAAATCTA TAAGAAGCTG AGAACTTCAT 
               
               
                   
               
               
                 11461 
                 CATTTGCCCT CAACCTACCA ACACTCCCCG AGGTAAAATT CCCTGAAGTT GATGTGTTAA 
               
               
                   
               
               
                 11521 
                 CAAAATATTC TCAACCAGAA GACTCCTTGA TTCCCTTTTT TGAGATAACC GTGCCTGAAT 
               
               
                   
               
               
                 11581 
                 CTCAGTTAAC TGTGTCCCAG TTCACGCTTC CAAAAAGTGT TTCAGATGGC ATTGCTGCTT 
               
               
                   
               
               
                 11641 
                 TGGATCTAAA TGCAGTAGCC AACAAGATCG CAGACTTTGA GTTGCCCACC ATCATCGTGC 
               
               
                   
               
               
                 11701 
                 CTGAGCAGAC CATTGAGATT CCCTCCATTA AGTTCTCTGT ACCTGCTGGA ATTGTCATTC 
               
               
                   
               
               
                 11761 
                 CTTCCTTTCA AGCACTGACT GCACGCTTTG AGGTAGACTC TCCCGTGTAT AATGCCACTT 
               
               
                   
               
               
                 11821 
                 GGAGTGCCAG TTTGAAAAAC AAAGCAGATT ATGTTGAAAC AGTCCTGGAT TCCACATGCA 
               
               
                   
               
               
                 11881 
                 GCTCAACCGT ACAGTTCCTA GAATATGAAC TAAATGTTTT GGGAACACAC AAAATCGAAG 
               
               
                   
               
               
                 11941 
                 ATGGTACGTT AGCCTCTAAG ACTAAAGGAA CATTTGCACA CCGTGACTTC AGTGCAGAAT 
               
               
                   
               
               
                 12001 
                 ATGAAGAAGA TGGCAAATAT GAAGGACTTC AGGAATGGGA AGGAAAAGCG CACCTCAATA 
               
               
                   
               
               
                 12061 
                 TCAAAAGCCC AGCGTTCACC GATCTCCATC TGCGCTACCA GAAAGACAAG AAAGGCATCT 
               
               
                   
               
               
                 12121 
                 CCACCTCAGC AGCCTCCCCA GCCGTAGGCA CCGTGGGCAT GGATATGGAT GAAGATGACG 
               
               
                   
               
               
                 12181 
                 ACTTTTCTAA ATGGAACTTC TACTACAGCC CTCAGTCCTC TCCAGATAAA AAACTCACCA 
               
               
                   
               
               
                 12241 
                 TATTCAAAAC TGAGTTGAGG GTCCGGGAAT CTGATGAGGA AACTCAGATC AAAGTTAATT 
               
               
                   
               
               
                 12301 
                 GGGAAGAAGA GGCAGCTTCT GGCTTGCTAA CCTCTCTGAA AGACAACGTG CCCAAGGCCA 
               
               
                   
               
               
                 12361 
                 CAGGGGTCCT TTATGATTAT GTCAACAAGT ACCACTGGGA ACACACAGGG CTCACCCTGA 
               
               
                   
               
               
                 12421 
                 GAGAAGTGTC TTCAAAGCTG AGAAGAAATC TGCAGAACAA TGCTGAGTGG GTTTATCAAG 
               
               
                   
               
               
                 12481 
                 GGGCCATTAG GCAAATTGAT GATATCGACG TGAGGTTCCA GAAAGCAGCC AGTGGCACCA 
               
               
                   
               
               
                 12541 
                 CTGGGACCTA CCAAGAGTGG AAGGACAAGG CCCAGAATCT GTACCAGGAA CTGTTGACTC 
               
               
                   
               
               
                 12601 
                 AGGAAGGCCA AGCCAGTTTC CAGGGACTCA AGGATAACGT GTTTGATGGC TTGGTACGAG 
               
               
                   
               
               
                 12661 
                 TTACTCAAGA ATTCCATATG AAAGTCAAGC ATCTGATTGA CTCACTCATT GATTTTCTGA 
               
               
                   
               
               
                 12721 
                 ACTTCCCCAG ATTCCAGTTT CCGGGGAAAC CTGGGATATA CACTAGGGAG GAACTTTGCA 
               
               
                   
               
               
                 12781 
                 CTATGTTCAT AAGGGAGGTA GGGACGGTAC TGTCCCAGGT ATATTCGAAA GTCCATAATG 
               
               
                   
               
               
                 12841 
                 GTTCAGAAAT ACTGTTTTCC TATTTCCAAG ACCTAGTGAT TACACTTCCT TTCGAGTTAA 
               
               
                   
               
               
                 12901 
                 GGAAACATAA ACTAATAGAT GTAATCTCGA TGTATAGGGA ACTGTTGAAA GATTTATCAA 
               
               
                   
               
               
                 12961 
                 AAGAAGCCCA AGAGGTATTT AAAGCCATTC AGTCTCTCAA GACCACAGAG GTGCTACGTA 
               
               
                   
               
               
                 13021 
                 ATCTTCAGGA CCTTTTACAA TTCATTTTCC AACTAATAGA AGATAACATT AAACAGCTGA 
               
               
                   
               
               
                 13081 
                 AAGAGATGAA ATTTACTTAT CTTATTAATT ATATCCAAGA TGAGATCAAC ACAATCTTCA 
               
               
                   
               
               
                 13141 
                 GTGATTATAT CCCATATGTT TTTAAATTGT TGAAAGAAAA CCTATGCCTT AATCTTCATA 
               
               
                   
               
               
                 13201 
                 AGTTCAATGA ATTTATTCAA AACGAGCTTC AGGAAGCTTC TCAAGAGTTA CAGCAGATCC 
               
               
                   
               
               
                 13261 
                 ATCAATACAT TATGGCCCTT CGTGAAGAAT ATTTTGATCC AAGTATAGTT GGCTGGACAG 
               
               
                   
               
               
                 13321 
                 TGAAATATTA TGAACTTGAA GAAAAGATAG TCAGTCTGAT CAAGAACCTG TTAGTTGCTC 
               
               
                   
               
               
                 13381 
                 TTAAGGACTT CCATTCTGAA TATATTGTCA GTGCCTCTAA CTTTACTTCC CAACTCTCAA 
               
               
                   
               
               
                 13441 
                 GTCAAGTTGA GCAATTTCTG CACAGAAATA TTCAGGAATA TCTTAGCATC CTTACCGATC 
               
               
                   
               
               
                 13501 
                 CAGATGGAAA AGGGAAAGAG AAGATTGCAG AGCTTTCTGC CACTGCTCAG GAAATAATTA 
               
               
                   
               
               
                 13561 
                 AAAGCCAGGC CATTGCGACG AAGAAAATAA TTTCTGATTA CCACCAGCAG TTTAGATATA 
               
               
                   
               
               
                 13621 
                 AACTGCAAGA TTTTTCAGAC CAACTCTCTG ATTACTATGA AAAATTTATT GCTGAATCCA 
               
               
                   
               
               
                 13681 
                 AAAGATTGAT TGACCTGTCC ATTCAAAACT ACCACACATT TCTGATATAC ATCACGGAGT 
               
               
                   
               
               
                 13741 
                 TACTGAAAAA GCTGCAATCA ACCACAGTCA TGAACCCCTA CATGAAGCTT GCTCCAGGAG 
               
               
                   
               
               
                 13801 
                 AACTTACTAT CATCCTCTAA TTTTTTAAAA GAAATCTTCA TTTATTCTTC TTTTCCAATT 
               
               
                   
               
               
                 13861 
                 GAACTTTCAC ATAGCACAGA AAAAATTCAA ACTGCCTATA TTGATAAAAC CATACAGTGA 
               
               
                   
               
               
                 13921 
                 GCCAGCCTTG CAGTAGGCAG TAGACTATAA GCAGAAGCAC ATATGAACTG GACCTGCACC 
               
               
                   
               
               
                 13981 
                 AAAGCTGGCA CCAGGGCTCG GAAGGTCTCT GAACTCAGAA GGATGGCATT TTTTGCAAGT 
               
               
                   
               
               
                 14041 
                 TAAAGAAAAT CAGGATCTGA GTTATTTTGC TAAACTTGGG GGAGGAGGAA CAAATAAATG 
               
               
                   
               
               
                 14101 
                 GAGTCTTTAT TGTGTATCAT A 
               
               
                   
               
            
           
           
               
            
               
                   HOMO SAPIENS  NUCLEAR RECEPTOR 
               
               
                 INTERACTING PROTEIN 1 (NRIP1), MRNA (GENE ACCESSION NM_003489) 
               
            
           
           
               
               
            
               
                 1 
                 GCAGGCGCCT TCGCGGACCG AGCCTGACGG AGCCGGAGGC TGGGAGCCGC GGCGGCCTGG 
               
               
                   
               
               
                 61 
                 GGAAGTGTTT GGATTGTGAG CTATTTCAGA ACTGTTCTCA GGACTCATTA TTTTAACATT 
               
               
                   
               
               
                 121 
                 TGGGAGAAAC ACAGCCAGAA GATGCACACT TGACTGAAGG AGGACAGGGA ATCTGAAGAC 
               
               
                   
               
               
                 181 
                 TCCGGATGAC ATCAGAGCTA CTTTTCAACA GCCTTCTCAA TTTTCTTTCT CAGAAAGCAG 
               
               
                   
               
               
                 241 
                 AGGCTCAGAG CTTGGAGACA GACGAACACT GATATTTGCA TTTAATGGGG AACAAAAGAT 
               
               
                   
               
               
                 301 
                 GAAGAAGGAA AAGGAATATA TTCACTAAGG ATTCTATCTG CTTACTGCTA CAGACCTATG 
               
               
                   
               
               
                 361 
                 TGTTAAGGAA TTCTTCTCCT CCTCCTTGCG TAGAAGTTGA TCAGCACTGT GGTCAGACTG 
               
               
                   
               
               
                 421 
                 CATTTATCTT GTCATTGCCA GAAGAAATCT TGGACAGAAT GTAACAGTAC GTCTCTCTCT 
               
               
                   
               
               
                 481 
                 GATTGCGATG GAAGGTGATA AACTGATACT CCTTTATTAA AGTTACATCG CACTCACCAC 
               
               
                   
               
               
                 541 
                 AGAAAACCAT TCTTTAAAGT GAATAGAAAC CAAGCCCTTG TGAACACTTC TATTGAACAT 
               
               
                   
               
               
                 601 
                 GACTCATGGA GAAGAGCTTG GCTCTGATGT GCACCAGGAT TCTATTGTTT TAACTTACCT 
               
               
                   
               
               
                 661 
                 AGAAGGATTA CTAATGCATC AGGCAGCAGG GGGATCAGGT ACTGCCGTTG ACAAAAAGTC 
               
               
                   
               
               
                 721 
                 TGCTGGGCAT AATGAAGAGG ATCAGAACTT TAACATTTCT GGCAGTGCAT TTCCCACCTG 
               
               
                   
               
               
                 781 
                 TCAAAGTAAT GGTCCAGTTC TCAATACACA TACATATCAG GGGTCTGGCA TGCTGCACCT 
               
               
                   
               
               
                 841 
                 CAAAAAAGCC AGACTGTTGC AGTCTTCTGA GGACTGGAAT GCAGCAAAGC GGAAGAGGCT 
               
               
                   
               
               
                 901 
                 GTCTGATTCT ATCATGAATT TAAACGTAAA GAAGGAAGCT TTGCTAGCTG GCATGGTTGA 
               
               
                   
               
               
                 961 
                 CAGTGTGCCT AAAGGCAAAC AGGATAGCAC ATTACTGGCC TCTTTGCTTC AGTCATTCAG 
               
               
                   
               
               
                 1021 
                 CTCTAGGCTG CAGACTGTTG CTCTGTCACA ACAAATCAGG CAGAGCCTCA AGGAGCAAGG 
               
               
                   
               
               
                 1081 
                 ATATGCCCTC AGTCATGATT CTTTAAAAGT GGAGAAGGAT TTAAGGTGCT ATGGTGTTGC 
               
               
                   
               
               
                 1141 
                 ATCAAGTCAC TTAAAAACTT TGTTGAAGAA AAGTAAAGTT AAAGATCAAA AGCCTGATAC 
               
               
                   
               
               
                 1201 
                 GAATCTTCCT GATGTGACTA AAAACCTCAT CAGAGATAGG TTTGCAGAGT CTCCTCATCA 
               
               
                   
               
               
                 1261 
                 TGTTGGACAA AGTGGAACAA AGGTCATGAG TGAACCGTTG TCATGTGCTG CAAGATTACA 
               
               
                   
               
               
                 1321 
                 GGCTGTTGCA AGCATGGTGG AAAAAAGGGC TAGTCCTGCC ACCTCACCTA AACCTAGTGT 
               
               
                   
               
               
                 1381 
                 TGCTTGTAGC CAGTTAGCAT TACTTCTGTC AAGCGAAGCC CATTTGCAGC AGTATTCTCG 
               
               
                   
               
               
                 1441 
                 AGAACACGCT TTAAAAACGC AAAATGCAAA TCAAGCAGCA AGTGAAAGAC TTGCTGCTAT 
               
               
                   
               
               
                 1501 
                 GGCCAGATTG CAAGAAAATG GCCAGAAGGA TGTTGGCAGT TACCAGCTCC CAAAAGGAAT 
               
               
                   
               
               
                 1561 
                 GTCAAGCCAT CTTAATGGTC AGGCAAGAAC ATCATCAAGC AAACTGATGG CTAGCAAAAG 
               
               
                   
               
               
                 1621 
                 TAGTGCTACA GTGTTTCAAA ATCCAATGGG TATCATTCCT TCTTCCCCTA AAAATGCAGG 
               
               
                   
               
               
                 1681 
                 TTATAAGAAC TCACTGGAAA GAAACAATAT AAAACAAGCT GCTAACAATA GTTTGCTTTT 
               
               
                   
               
               
                 1741 
                 ACATCTTCTT AAAAGCCAGA CTATACCTAA GCCAATGAAT GGACACAGTC ACAGTGAGAG 
               
               
                   
               
               
                 1801 
                 AGGAAGCATT TTTGAGGAAA GTAGTACACC TACAACTATT GATGAATATT CAGATAACAA 
               
               
                   
               
               
                 1861 
                 TCCTAGTTTT ACAGATGACA GCAGTGGTGA TGAAAGTTCT TATTCCAACT GTGTTCCCAT 
               
               
                   
               
               
                 1921 
                 AGACTTGTCT TGCAAACACC GAACTGAAAA ATCAGAATCT GACCAACCTG TTTCCCTGGA 
               
               
                   
               
               
                 1981 
                 TAACTTCACT CAATCCTTGC TAAACACTTG GGATCCAAAA GTCCCAGATG TAGATATCAA 
               
               
                   
               
               
                 2041 
                 AGAAGATCAA GATACCTCAA AGAATTCTAA GCTAAACTCA CACCAGAAAG TAACACTTCT 
               
               
                   
               
               
                 2101 
                 TCAATTGCTA CTTGGCCATA AGAATGAAGA AAATGTAGAA AAAAACACCA GCCCTCAGGG 
               
               
                   
               
               
                 2161 
                 AGTACACAAT GATGTGAGCA AGTTCAATAC ACAAAATTAT GCAAGGACTT CTGTGATAGA 
               
               
                   
               
               
                 2221 
                 AAGCCCCAGT ACAAATCGGA CTACTCCAGT GAGCACTCCA CCTTTACTTA CATCAAGCAA 
               
               
                   
               
               
                 2281 
                 AGCAGGGTCT CCCATCAATC TCTCTCAACA CTCTCTGGTC ATCAAATGGA ATTCCCCACC 
               
               
                   
               
               
                 2341 
                 ATATGTCTGC AGTACTCAGT CTGAAAAGCT AACAAATACT GCATCTAACC ACTCAATGGA 
               
               
                   
               
               
                 2401 
                 CCTTACAAAA AGCAAAGACC CACCAGGAGA GAAACCAGCC CAAAATGAAG GTGCACAGAA 
               
               
                   
               
               
                 2461 
                 CTCTGCAACG TTTAGTGCCA GTAAGCTGTT ACAAAATTTA GCACAATGTG GAATGCAGTC 
               
               
                   
               
               
                 2521 
                 ATCCATGTCA GTGGAAGAGC AGAGACCCAG CAAACAGCTG TTAACTGGAA ACACAGATAA 
               
               
                   
               
               
                 2581 
                 ACCGATAGGT ATGATTGATA GATTAAATAG CCCTTTGCTC TCAAATAAAA CAAATGCAGT 
               
               
                   
               
               
                 2641 
                 TGAAGAAAAT AAAGCATTTA GTAGTCAACC AACAGGTCCT GAACCAGGGC TTTCTGGTTC 
               
               
                   
               
               
                 2701 
                 TGAAATAGAA AATCTGCTTG AAAGACGTAC TGTCCTCCAG TTGCTCCTGG GGAACCCCAA 
               
               
                   
               
               
                 2761 
                 CAAAGGGAAG AGTGAAAAAA AAGAGAAAAC TCCCTTAAGA GATGAAAGTA CTCAGGAACA 
               
               
                   
               
               
                 2821 
                 CTCAGAGAGA GCTTTAAGTG AACAAATACT GATGGTGAAA ATAAAATCTG AGCCTTGTGA 
               
               
                   
               
               
                 2881 
                 TGACTTACAA ATTCCTAACA CAAATGTGCA CTTGAGCCAT GATGCTAAGA GTGCCCCATT 
               
               
                   
               
               
                 2941 
                 CTTGGGTATG GCTCCTGCTG TGCAGAGAAG CGCACCTGCC TTACCAGTGT CCGAAGACTT 
               
               
                   
               
               
                 3001 
                 TAAATCGGAG CCTGTTTCAC CTCAGGATTT TTCTTTCTCC AAGAATGGTC TGCTAAGTCG 
               
               
                   
               
               
                 3061 
                 ATTGCTAAGA CAAAATCAAG ATAGTTACCT GGCAGATGAT TCAGACAGGA GTCACAGAAA 
               
               
                   
               
               
                 3121 
                 TAATGAAATG GCACTTCTAG AATCAAAGAA TCTTTGCATG GTCCCTAAGA AAAGGAAGCT 
               
               
                   
               
               
                 3181 
                 TTATACTGAG CCATTAGAAA ATCCATTTAA AAAGATGAAA AACAACATTG TTGATGCTGC 
               
               
                   
               
               
                 3241 
                 AAACAATCAC AGTGCCCCAG AAGTACTGTA TGGGTCCTTG CTTAACCAGG AAGAGCTGAA 
               
               
                   
               
               
                 3301 
                 ATTTAGCAGA AATGATCTTG AATTTAAATA TCCTGCTGGT CATGGCTCAG CCAGCGAAAG 
               
               
                   
               
               
                 3361 
                 TGAACACAGG AGTTGGGCCA GAGAGAGCAA AAGCTTTAAT GTTCTGAAAC AGCTGCTTCT 
               
               
                   
               
               
                 3421 
                 CTCAGAAAAC TGTGTGCGAG ATTTGTCCCC GCACAGAAGT AACTCTGTGG CTGACAGTAA 
               
               
                   
               
               
                 3481 
                 AAAGAAAGGA CACAAAAATA ATGTGACCAA CAGCAAACCT GAATTTAGCA TTTCTTCTTT 
               
               
                   
               
               
                 3541 
                 AAATGGACTG ATGTACAGTT CCACTCAGCC CAGCAGTTGC ATGGATAACA GGACATTTTC 
               
               
                   
               
               
                 3601 
                 ATACCCAGGT GTAGTAAAAA CTCCTGTGAG TCCTACTTTC CCTGAGCACT TGGGCTGTGC 
               
               
                   
               
               
                 3661 
                 AGGGTCTAGA CCAGAATCTG GGCTTTTGAA TGGGTGTTCC ATGCCCAGTG AGAAAGGACC 
               
               
                   
               
               
                 3721 
                 CATTAAGTGG GTTATCACTG ATGCGGAGAA GAATGAGTAT GAAAAAGACT CTCCAAGATT 
               
               
                   
               
               
                 3781 
                 GACCAAAACC AACCCAATAC TATATTACAT GCTTCAAAAA GGAGGCAATT CTGTTACCAG 
               
               
                   
               
               
                 3841 
                 TCGAGAAACA CAAGACAAGG ACATTTGGAG GGAGGCTTCA TCTGCTGAAA GTGTCTCACA 
               
               
                   
               
               
                 3901 
                 GGTCACAGCC AAAGAAGAGT TACTTCCTAC TGCAGAAACG AAAGCTTCTT TCTTTAATTT 
               
               
                   
               
               
                 3961 
                 AAGAAGCCCT TACAATAGCC ATATGGGAAA TAATGCTTCT CGCCCACACA GCGCAAATGG 
               
               
                   
               
               
                 4021 
                 AGAAGTTTAT GGACTTCTGG GAAGCGTGCT AACGATAAAG AAAGAATCAG AATAAAATGT 
               
               
                   
               
               
                 4081 
                 ACCTGCCATC CAGTTTTGGA TCTTTTTAAA ACTAATGAGT ATGAACTTGA GATCTGTATA 
               
               
                   
               
               
                 4141 
                 AATAAGAGCA TGATTTGAAA AAAAGCATGG TATAATTGAA ACTTTTTTCA TTTTGAAAAG 
               
               
                   
               
               
                 4201 
                 TATTGGTTAC TGGTGATGTT GAAATATGCA TACTAATTTT TGCTTAACAT TAGATGTCAT 
               
               
                   
               
               
                 4261 
                 GAGGAAACTA CTGAACTAGC AATTGGTTGT TTAACACTTC TGTATGCATC AGATAACAAC 
               
               
                   
               
               
                 4321 
                 TGTGAGTAGC CTATGAATGA AATTCTTTTA TAAATATTAG GCATAAATTA AAATGTAAAA 
               
               
                   
               
               
                 4381 
                 CTCCATTCAT AGTGGATTAA TGCATTTTGC TGCCTTTATT AGGGTACTTT ATTTTGCTTT 
               
               
                   
               
               
                 4441 
                 TCAGAAGTCA GCCTACATAA CACATTTTTA AAGTCTAAAC TGTTAAACAA CTCTTTAAAG 
               
               
                   
               
               
                 4501 
                 GATAATTATC CAATAAAAAA AAACCTAGTG CTGATTCACA GCTTATTATC CAATTCAAAA 
               
               
                   
               
               
                 4561 
                 ATAAATTAGA AAAATATATG CTTACATTTT TCACTTTTGC TAAAAAGAAA AAAAAAAGGT 
               
               
                   
               
               
                 4621 
                 GTTTATTTTT AACTCTTGGA AGAGGTTTTG TGGTTCCCAA TGTGTCTGTC CCACCCTGAT 
               
               
                   
               
               
                 4681 
                 CCTTTTCAAT ATATATTTCT TTAAACCTTG TGCTACTTAG TAAAAATTGA TTACAATTGA 
               
               
                   
               
               
                 4741 
                 GGGAAGTTTG ATAGATCCTT TAAAAAAAAG GCAGATTTCC ATTTTTTGTA TTTTAACTAC 
               
               
                   
               
               
                 4801 
                 TTTACTAAAT TAATACTCCT CCTTTTACAG AATTAGAAAA GTTAACATTT ATCTTTAGGT 
               
               
                   
               
               
                 4861 
                 GGTTTCCTGA AAAGTTGAAT ATTTAAGAAA TTGTTTTTAA CAGAAGCAAA ATGGCTTTTC 
               
               
                   
               
               
                 4921 
                 TTTGGACAGT TTTCACCATC TCTTGTAAAA GTTAATTCTC ACCATTCCTG TGGTACCTGC 
               
               
                   
               
               
                 4981 
                 GAGTGTTATG ACCAGGATTC CTTAAACCTG AACTCAGACC ACTTGCATTA GAACCATCTG 
               
               
                   
               
               
                 5041 
                 GAGCACTTGT TTTAAAATGC AGATTCATAG GCAGCATCTC AGATCTACAG AACAAGAATC 
               
               
                   
               
               
                 5101 
                 TCTGCTAAGT GGACCTGGAA TCTTCCATCT GCATCTTAAC ATGCTCTCTA GGTGTTTCTT 
               
               
                   
               
               
                 5161 
                 GTGTTTGAGA ACCATGACTT ATGACTTTCC TCAGAACATG AGACTGTAAA ACAAAAACAA 
               
               
                   
               
               
                 5221 
                 AAAACTATGT GATGCCTCTA TTTTCCCCAA TACAGTCACA CATCAGCTCA AAATTTGCAA 
               
               
                   
               
               
                 5281 
                 TATTGTAGTT CATATATTAC CGTTATGTCT TTGGAAATCG GGTTCAGAAC ACTTTTTATG 
               
               
                   
               
               
                 5341 
                 ACAAAAATTG GGTGGAGGGG ATAACTTTCA TATCTGGCTC AACATCTCAG GAAAATCTGT 
               
               
                   
               
               
                 5401 
                 GATTATTTGT GTGTTCTAAT GAGTAACATC TACTTAGTTA GCCTTAGGGA TGGAAAAACA 
               
               
                   
               
               
                 5461 
                 GGGCCACTTA CCAAACTCAG GTGATTCCAG GATGGTTTGG AAACTTCTCC TGAATGCATC 
               
               
                   
               
               
                 5521 
                 CTTAACCTTT ATTAAAACCA TTGTCCTAAG AACAATGCCA ACAAAGCTTA CAACATTTAG 
               
               
                   
               
               
                 5581 
                 TTTAAACCCA AGAAGGGCAC TAAACTCAGA TTGACTAAAT AAAAAGTACA AAGGGCACAT 
               
               
                   
               
               
                 5641 
                 ATACGTGACA GAATTGTACA CAATCACTCC ATTGGATCTT TTACTTTAAA GTAGTGATGA 
               
               
                   
               
               
                 5701 
                 AAAGTACATG TTGATACTGT CTTAGAAGAA ATTAATATAT TAGTGAAGCC ACATGGGGTT 
               
               
                   
               
               
                 5761 
                 TCAGTTGCGA AACAGGTCTG TTTTTATGTT CAGTTTGTAC AATCCACAAT TCATTCACCA 
               
               
                   
               
               
                 5821 
                 GATATTTTGT TCTTAATTGT GAACCAGGTT AGCAAATGAC CTATCAAAAA TTATTCTATA 
               
               
                   
               
               
                 5881 
                 ATCACTACTA GTTAGGATAT TGATTTAAAA TTGTTCTACT TGAAGTGGTT TCTAAGATTT 
               
               
                   
               
               
                 5941 
                 TTATATTAAA AATAGGTGTG ATTTCCTAAT ATGATCTAAA ACCCTAAATG GTTATTTTTC 
               
               
                   
               
               
                 6001 
                 CTCAGAATGA TTTGTAAATA GCTACTGGAA ATATTATACA GTAATAGGAG TGGGTATTAT 
               
               
                   
               
               
                 6061 
                 GCAACATCAT GGAGAAGTGA AGGCATAGGC TTATTCTGAC ATAAAATTCC ACTGGCCAGT 
               
               
                   
               
               
                 6121 
                 TGAATATATT CTATTCCATG TCCATACTAT GACAATCTTA TTGTCAACAC TATATAAATA 
               
               
                   
               
               
                 6181 
                 AGCTTTTAAA CAAGTCATTT TTCTTGATCG TTGTGGAAGG TTTGGAGCCT TAGAGGTATG 
               
               
                   
               
               
                 6241 
                 TCAGAAAAAA TATGTTGGTA TTCTCCCTTG GGTAGGGGGA AATGACCTTT TTACAAGAGA 
               
               
                   
               
               
                 6301 
                 GTGAAATTTA GGTCAGGGAA AAGACCAAGG GCCAGCATTG CTACTTTTGT GTGTGTGTGT 
               
               
                   
               
               
                 6361 
                 GTGGGTTTTG TTTTGTTTTT TTGGTTGGCT GGTTGTTTTC GTTGTTGTTA ACAAAGGAAT 
               
               
                   
               
               
                 6421 
                 GAGAATATGT AATACTTAAA TAAACATGAC CACGAAGAAT GCTGTTCTGA TTTACTAGAG 
               
               
                   
               
               
                 6481 
                 AATGTTCCCA ATTTGAATTT AGGGTGATTT TAAAGAACAG TGAGAAAGGG CATACATCCA 
               
               
                   
               
               
                 6541 
                 CAGATTCACT TTGTTTATGC ATATGTAGAT ACAAGGATGC ACATATACAC ATTTTCAAGG 
               
               
                   
               
               
                 6601 
                 ACTATTTTAG ATATCTAGAC AATTTCTTCT AATAAAGTCA TTTGTGAAAG GGTACTACAG 
               
               
                   
               
               
                 6661 
                 CTTATTGACA TCAGTAAGGT AGCATTCATT ACCTGTTTAT TCTCTGCTGC ATCTTACAGA 
               
               
                   
               
               
                 6721 
                 AGAGTAAACT GGTGAGAGTA TATATTTTAT ATATATATAT ATATATATAT ATATAATATG 
               
               
                   
               
               
                 6781 
                 TATATATATA TATATTGACT TGTTACATGA AGATGTTAAA ATCGGTTTTT AAAGGTGATG 
               
               
                   
               
               
                 6841 
                 TAAATAGTGA TTTCCTTAAT GAAAAATACA TATTTTGTAT TGTTCTAATG CAACAGAAAA 
               
               
                   
               
               
                 6901 
                 GCCTTTTAAT CTCTTTGGTT CCTGTATATT CCATGTATAA GTGTAAATAT AATCAGACAG 
               
               
                   
               
               
                 6961 
                 GTTTAAAAGT TGTGCATGTA TGTATACAGT TGCAAGTCTG GACAAATGTA TAGAATAAAC 
               
               
                   
               
               
                 7021 
                 CTTTTATTTA AGTTGTGATT ACCTGCTGCA TGAAAAGTGC ATGGGGGACC CTGTGCATCT 
               
               
                   
               
               
                 7081 
                 GTGCATTTGG CAAAATGTCT TAACAAATCA GATCAGATGT TCATCCTAAC ATGACAGTAT 
               
               
                   
               
               
                 7141 
                 TCCATTTCTG GACATGACGT CTGTGGTTTA AGCTTTGTGA AAGAATGTGC TTTGATTCGA 
               
               
                   
               
               
                 7201 
                 AGGGTCTTAA AGAATTTTTT TAATCGTCAA CCACTTTTAA ACATAAAGAA TTCACACAAC 
               
               
                   
               
               
                 7261 
                 TACTTTCATG AATTTTTTAA TCCCATTGCA AACATTATTC CAAGAGTATC CCAGTATTAG 
               
               
                   
               
               
                 7321 
                 CAATACTGGA ATATAGGCAC ATTACCATTC ATAGTAAGAA TTCTGGTGTT TACACAACCA 
               
               
                   
               
               
                 7381 
                 AATTTGATGC GATCTGCTCA GTAATATAAT TTGCCATTTT TATTAGAAAT TTAATTTCTT 
               
               
                   
               
               
                 7441 
                 CATGTGATGT CATGAAACTG TACATACTGC AGTGTGAATT TTTTTGTTTT GTTTTTTAAT 
               
               
                   
               
               
                 7501 
                 CTTTTAGTGT TTACTTCCTG CAGTGAATTT GAATAAATGA GAAAAAATGC ATTGTC 
               
               
                   
               
            
           
           
               
            
               
                   HOMO SAPIENS  B-CELL CLL/LYMPHOMA 11B (BCL11B), 
               
               
                 TRANSCRIPT VARIANT 2, MRNA (GENE ACCESSION NM_022898) 
               
            
           
           
               
               
            
               
                 1 
                 TGCGCTTTCC ACCTACCAGA CCCTGAAAGA AAGTGTCAGG AGCCGGTGCA AAACCCAGTT 
               
               
                   
               
               
                 61 
                 TAAGTTCAAG AAGACATTTG CAAGTGCAAG AGGCCAAGCA GTTTGAAGAA GTGTAAGAGA 
               
               
                   
               
               
                 121 
                 TTTTTTTTCC TTCGAAAGAA TATATTTTTA AAGAAACCAG CCAGTCCGCG GAAAGCAACA 
               
               
                   
               
               
                 181 
                 GCAGTTTTTT TTTTTTTTGC CTCTTTTTCT TATTTTAGAT CGAGAGGTTT TTCTTGCTTT 
               
               
                   
               
               
                 241 
                 TCTTCCCTTT TTTTTCTTTT TGCAAACAAA ACAAAAAACA GCATAGAAGA AAGAGCAAAA 
               
               
                   
               
               
                 301 
                 TAAAGAAGAA GAAGAGGAGG AAGAGAGGGA AAGAGAGGAA GGGAAAAAAA ACACCAACCC 
               
               
                   
               
               
                 361 
                 GGGCAGAGGA GGAGGTGCGG CGGCGGCGGC GGCGGCGGCA GCGGCGGCAG CGGCGCGGCG 
               
               
                   
               
               
                 421 
                 GCGGCTCGGA CCCCCTCCCC CGGCTCCCCC CATCAGTGCA GCTCTCCGGG CGATGCCAGA 
               
               
                   
               
               
                 481 
                 ATAGATGCCG GGGCAATGTC CCGCCGCAAA CAGGGCAACC CGCAGCACTT GTCCCAGAGG 
               
               
                   
               
               
                 541 
                 GAGCTCATCA CCCCAGAGGC TGACCATGTG GAGGCCGCCA TCCTCGAAGA AGACGAGGGT 
               
               
                   
               
               
                 601 
                 CTGGAGATAG AGGAGCCAAG TGGCCTGGGG CTGATGGTGG GTGGCCCCGA CCCTGACCTG 
               
               
                   
               
               
                 661 
                 CTCACCTGTG GCCAGTGTCA AATGAACTTC CCCTTGGGGG ACATCCTGGT TTTTATAGAG 
               
               
                   
               
               
                 721 
                 CACAAAAGGA AGCAGTGTGG CGGCAGCTTG GGTGCCTGCT ATGACAAGGC CCTGGACAAG 
               
               
                   
               
               
                 781 
                 GACAGCCCGC CACCCTCCTC ACGCTCCGAG CTCAGGAAAG TGTCCGAGCC GGTGGAGATC 
               
               
                   
               
               
                 841 
                 GGGATCCAAG TCACCCCCGA CGAAGATGAC CACCTGCTCT CACCCACGAA AGGCATCTGT 
               
               
                   
               
               
                 901 
                 CCCAAGCAGG AGAACATTGC AGGTAAAGAT GAGCCTTCCA GCTACATTTG CACAACATGC 
               
               
                   
               
               
                 961 
                 AAGCAGCCCT TCAACAGCGC GTGGTTCCTG CTGCAGCACG CGCAGAACAC GCACGGCTTC 
               
               
                   
               
               
                 1021 
                 CGCATCTACC TGGAGCCCGG GCCGGCCAGC AGCTCGCTCA CGCCGCGGCT CACCATCCCG 
               
               
                   
               
               
                 1081 
                 CCGCCGCTCG GGCCGGAGGC CGTGGCGCAG TCCCCGCTCA TGAATTTCCT GGGCGACAGC 
               
               
                   
               
               
                 1141 
                 AACCCCTTCA ACCTGCTGCG CATGACGGGC CCCATCCTGC GGGACCACCC GGGCTTCGGC 
               
               
                   
               
               
                 1201 
                 GAGGGCCGCC TGCCGGGCAC GCCGCCTCTC TTCAGTCCCC CGCCGCGCCA CCACCTGGAC 
               
               
                   
               
               
                 1261 
                 CCGCACCGCC TCAGTGCCGA GGAGATGGGG CTCGTCGCCC AGCACCCCAG TGCCTTCGAC 
               
               
                   
               
               
                 1321 
                 CGAGTCATGC GCCTGAACCC CATGGCCATC GACTCGCCCG CCATGGACTT CTCGCGGCGG 
               
               
                   
               
               
                 1381 
                 CTCCGCGAGC TGGCGGGCAA CAGCTCCACG CCGCCGCCCG TGTCCCCGGG CCGCGGCAAC 
               
               
                   
               
               
                 1441 
                 CCTATGCACC GGCTCCTGAA CCCCTTCCAG CCCAGCCCCA AGTCCCCGTT CCTGAGCACG 
               
               
                   
               
               
                 1501 
                 CCGCCGCTGC CGCCCATGCC CCCTGGCGGC ACGCCGCCCC CGCAGCCGCC AGCCAAGAGC 
               
               
                   
               
               
                 1561 
                 AAGTCGTGCG AGTTCTGCGG CAAGACCTTC AAGTTCCAGA GCAATCTCAT CGTGCACCGG 
               
               
                   
               
               
                 1621 
                 CGCAGTCACA CGGGCGAGAA GCCCTACAAG TGCCAGCTGT GCGACCACGC GTGCTCGCAG 
               
               
                   
               
               
                 1681 
                 GCCAGCAAGC TCAAGCGCCA CATGAAGACG CACATGCACA AGGCCGGCTC GCTGGCCGGC 
               
               
                   
               
               
                 1741 
                 CGCTCCGACG ACGGGCTCTC GGCCGCCAGC TCCCCCGAGC CCGGCACCAG CGAGCTGGCG 
               
               
                   
               
               
                 1801 
                 GGCGAGGGCC TCAAGGCGGC CGACGGTGAC TTCCGCCACC ACGAGAGCGA CCCGTCGCTG 
               
               
                   
               
               
                 1861 
                 GGCCACGAGC CGGAGGAGGA GGACGAGGAG GAGGAGGAGG AGGAGGAGGA GCTGCTACTG 
               
               
                   
               
               
                 1921 
                 GAGAACGAGA GCCGGCCCGA GTCGAGCTTC AGCATGGACT CGGAGCTGAG CCGCAACCGC 
               
               
                   
               
               
                 1981 
                 GAGAACGGCG GTGGTGGGGT GCCCGGGGTC CCGGGCGCGG GGGGCGGCGC GGCCAAGGCG 
               
               
                   
               
               
                 2041 
                 CTGGCTGACG AGAAGGCGCT GGTGCTGGGC AAGGTCATGG AGAACGTGGG CCTAGGCGCA 
               
               
                   
               
               
                 2101 
                 CTGCCGCAGT ACGGCGAGCT CCTGGCCGAC AAGCAGAAGC GCGGCGCCTT CCTGAAGCGT 
               
               
                   
               
               
                 2161 
                 GCGGCGGGCG GCGGGGACGC GGGCGACGAC GACGACGCGG GCGGCTGCGG GGACGCGGGC 
               
               
                   
               
               
                 2221 
                 GCGGGCGGCG CGGTCAACGG GCGCGGGGGC GGCTTCGCGC CAGGCACCGA GCCCTTCCCC 
               
               
                   
               
               
                 2281 
                 GGGCTCTTCC CGCGCAAGCC CGCGCCGCTG CCCAGCCCCG GGCTCAACAG CGCCGCCAAG 
               
               
                   
               
               
                 2341 
                 CGCATCAAGG TGGAGAAGGA CCTGGAGCTG CCGCCCGCCG CGCTCATCCC GTCCGAGAAC 
               
               
                   
               
               
                 2401 
                 GTGTACTCGC AGTGGCTGGT GGGCTACGCG GCGTCGCGGC ACTTCATGAA GGACCCCTTC 
               
               
                   
               
               
                 2461 
                 CTGGGCTTCA CGGACGCACG ACAGTCGCCC TTCGCCACGT CGTCCGAGCA CTCGTCCGAG 
               
               
                   
               
               
                 2521 
                 AACGGCAGCC TGCGCTTCTC CACGCCGCCC GGGGACCTGC TGGACGGCGG CCTCTCGGGC 
               
               
                   
               
               
                 2581 
                 CGCAGCGGCA CGGCCAGCGG AGGCAGCACC CCGCACCTGG GCGGCCCGGG CCCCGGGCGG 
               
               
                   
               
               
                 2641 
                 CCCAGCTCCA AGGAGGGCCG CCGCAGCGAC ACGTGCGAGT ACTGCGGCAA GGTGTTCAAG 
               
               
                   
               
               
                 2701 
                 AACTGCAGCA ACTTGACGGT GCACCGGCGG AGCCACACCG GCGAGCGGCC TTACAAGTGC 
               
               
                   
               
               
                 2761 
                 GAGCTGTGCA ACTACGCGTG CGCGCAGAGC AGCAAGCTCA CGCGCCACAT GAAGACGCAC 
               
               
                   
               
               
                 2821 
                 GGGCAGATCG GCAAGGAGGT GTACCGCTGC GACATCTGCC AGATGCCCTT CAGCGTCTAC 
               
               
                   
               
               
                 2881 
                 AGCACCCTGG AGAAACACAT GAAAAAGTGG CACGGCGAGC ACTTGCTGAC TAACGACGTC 
               
               
                   
               
               
                 2941 
                 AAAATCGAGC AGGCCGAGAG GAGCTAAGCG CGCGGGCCCC GGCGCCCCGC ACCTGTACAG 
               
               
                   
               
               
                 3001 
                 TGGAACCGTT GCCAACCGAG AGAATGCTGA CCTGACTTGC CTCCGTGTCA CCGCCACCCC 
               
               
                   
               
               
                 3061 
                 GCACCCCGCG TGTCCCCGGG GCCCAGGGGA GGCGGCACTC CAACCTAACC TGTGTCTGCG 
               
               
                   
               
               
                 3121 
                 AAGTCCTATG GAAACCCGAG GGTTGATTAA GGCAGTACAA ATTGTGGAGC CTTTTAACTG 
               
               
                   
               
               
                 3181 
                 TGCAATAATT TCTGTATTTA TTGGGTTTTG TAATTTTTTT GGCATGTGCA GGTACTTTTT 
               
               
                   
               
               
                 3241 
                 ATTATTATTT TTTCTGTTTG AATTCCTTTA AGAGATTTTG TTGGGTATCC ATCCCTTCTT 
               
               
                   
               
               
                 3301 
                 TGTTTTTTTT TTAACCCGGT AGTAGCCTGA GCAATGACTC GCAAGCAATG TTAGAGGGGA 
               
               
                   
               
               
                 3361 
                 AGCATATCTT TTAAATTATA ATTTGGGGGG AGGGGTGGTG CTGCTTTTTT GAAATTTAAG 
               
               
                   
               
               
                 3421 
                 CTAAGCATGT GTAATTTCTT GTGAAGAAGC CAACACTCAA ATGACTTTTA AAGTTGTTTA 
               
               
                   
               
               
                 3481 
                 CTTTTTCATT CCTTCCTTTT TTTTGTCCTG AAATAAAAAG TGGCATGCAG TTTTTTTTTT 
               
               
                   
               
               
                 3541 
                 AATTATTTTT TAATTTTTTT TTTGGTTTTT GTTTTTGGGG TGGGGGGTGT GGATGTACAG 
               
               
                   
               
               
                 3601 
                 CGGATAACAA TCTTTCAAGT CGTAGCACTT TGTTTCAGAA CTGGAATGGA GATGTAGCAC 
               
               
                   
               
               
                 3661 
                 TCATGTCGTC CCGAGTCAAG CGGCCTTTTC TGTGTTGATT TCGGCTTTCA TATTACATAA 
               
               
                   
               
               
                 3721 
                 GGGAAACCTT GAGTGGTGGT GCTGGGGGAG GCACCCCACA GACTCAGCGC CGCCAGAGAT 
               
               
                   
               
               
                 3781 
                 AGGGTTTTTG GAGGGCTCCT CTGGGAAATG GCCCGACAGC ATTCTGAGGT TGTGCATGAC 
               
               
                   
               
               
                 3841 
                 CAGCAGATAC TATCCTGTTG GTGTGCCCTG GGGTGCCATG GCTGCTATTC GCTGTAGATT 
               
               
                   
               
               
                 3901 
                 AGGCTACATA AAATGGGCTG AGGGTACCTT TTTGGGGAGA TGGGGTGGCC TGCAGTGACA 
               
               
                   
               
               
                 3961 
                 CAGAAAGGAA GAAACTAGCG GTGTTCTTTT AGGCGTTTTC TGGCTTGACG GCTTCTCTCT 
               
               
                   
               
               
                 4021 
                 TTTTTTAAAT CACCCCCACC ACATAAATCT CAAATCCTAT GTTGCTACAA GGGGTCATCC 
               
               
                   
               
               
                 4081 
                 ATCATTTCCC AAGCAGACGA ATGCCCTAAT TAATTGAAGT TAGTGTTCTC TCATTTAATG 
               
               
                   
               
               
                 4141 
                 CACACTGATG ATATTGTAGG GATGGGTGGG GTGGGGATCT TGCAAATTTC TATTCTCTTT 
               
               
                   
               
               
                 4201 
                 TACTGAAAAA GCAGGGGATG AGTTCCATCA GAAGGTGCCC AGCGCTACTT CCCAGGTTTT 
               
               
                   
               
               
                 4261 
                 TATTTTTTTT TTCCTATCTC ATTAGGTTGG AAGGTACTAA ATATTGAACT GTTAAGATTA 
               
               
                   
               
               
                 4321 
                 GACATTTGAA TTCTGTTGAC CCGCACTTTA AAGCTTTTGT TTGCATTTAA ATTAAATGGC 
               
               
                   
               
               
                 4381 
                 TTCTAAACAA GAAATTGCAG CATATTCTTC TCTTTGGCCC AGAGGTGGGT TAAACTGTAA 
               
               
                   
               
               
                 4441 
                 GGGACAGCTG AGATTGAGTG TCAGTATTGC TAAGCGTGGC ATTCACAATA CTGGCACTAT 
               
               
                   
               
               
                 4501 
                 AAAGAACAAA ATAAAATAAT AATTTATAGG ACAGTTTTTC TACTGCCATT CAATTTGATG 
               
               
                   
               
               
                 4561 
                 TGAGTGCCTT GAAAACTGAT CTTCCTATTT GAGTCTCTTG AGACAAATGC AAAACTTTTT 
               
               
                   
               
               
                 4621 
                 TTTTGAAATG AAAAGACTTT TTAAAAAAGT AAAACAAGAA AAGTACATTC TTTAGAAACT 
               
               
                   
               
               
                 4681 
                 AACAAAGCCA CATTTACTTT AAGTAAAAAA AAAAAAAATT CTGGTTGAAG ATAGAGGATA 
               
               
                   
               
               
                 4741 
                 TGAAATGCCA TAAGACCCAA TCAAATGAAG AAATAAACCC AGCACAACCT TGGACATCCA 
               
               
                   
               
               
                 4801 
                 TTAGCTGAAT TATCCTCAGC CCCTTTTGTT TTTGGGACAA CGCTGCTTAG ATATGGAGTG 
               
               
                   
               
               
                 4861 
                 GAGGTGATTT ACTGCTGAAT TAAAACTCAA GTGACACAAG TTACAAGTTG ATATCGTTGA 
               
               
                   
               
               
                 4921 
                 ATGAAAAGCA AAACAAAAAC AATTCAGGAA CAACGGCTAA TTTTTTCTAA AGTTAAATTT 
               
               
                   
               
               
                 4981 
                 AGTGCACTCT GTCTTAAAAA TACGTTTACA GTATTGGGTA CATACAAGGG TAAAAAAAAA 
               
               
                   
               
               
                 5041 
                 ATTGTGTGTA TGTGTGTTGG AGCGATCTTT TTTTTTCAAA GTTTGCTTAA TAGGTTATAC 
               
               
                   
               
               
                 5101 
                 AAAAATGCCA CAGTGGCCGC GTGTATATTG TTTTCTTTTG GTGACGGGGT TTTAGTATAT 
               
               
                   
               
               
                 5161 
                 ATTATATATA TTAAAATTTC TTGATTACTG TAAAAGTGGA CCAGTATTTG TAATAATCGA 
               
               
                   
               
               
                 5221 
                 GAATGCCTGG GCATTTTACA AAACAAGAAA AAAAATACCC TTTTCTTTTC CTTGAAAATG 
               
               
                   
               
               
                 5281 
                 TTGCAGTAAA ATTTAAATGG TGGGTCTATA AATTTGTTCT TGTTACAGTA ACTGTAAAGT 
               
               
                   
               
               
                 5341 
                 CGGAGTTTTA GTAAATTTTT TTCTGCCTTG GGTGTTGAAT TTTTATTTCA AAAAAAATGT 
               
               
                   
               
               
                 5401 
                 ATAGAAACTT GTATTTGGGG ATTCAAAGGG GATTGCTACA CCATGTAGAA AAAGTATGTA 
               
               
                   
               
               
                 5461 
                 GAAAAAAAGT GCTTAATATT GTTATTGCTT TGCAGAAAAA AAAAAAATCA CATTTCTGAC 
               
               
                   
               
               
                 5521 
                 CTGTACTTAT TTTTCTCTTC CCGCCTCCCT CTGGAATGGA TATATTGGTT GGTTCATATG 
               
               
                   
               
               
                 5581 
                 ATGTAGGCAC TTGCTGTATT TTTACTGGAG CTCGTAATTT TTTAACTGTA AGCTTGTCCT 
               
               
                   
               
               
                 5641 
                 TTTAAAGGGA TTTAATGTAC CTTTTTGTTA GTGAATTTGG AAATAAAAAG AAAAAAAAAA 
               
               
                   
               
               
                 5701 
                 CAAAAACAAA CAGGCTGCCA TAATATATTT TTTTAATTTG GCAGGATAAA ATATTGCAAA 
               
               
                   
               
               
                 5761 
                 AAAAACACAT TTGTATGTTA AGTCCTATTG TACAGGAGAA AAAGGGTTGT TTGACAACCT 
               
               
                   
               
               
                 5821 
                 TTGAGAAAAA GAAACAAAAG GAAGTAGTTA AATGCTTTGG TTCACAAATC ATTTAGTTGT 
               
               
                   
               
               
                 5881 
                 ATATATTTTT TGTCGGAATT GGCCTACACA GAGAACCGTT CGTGTTGGGC TTCTCTCTGA 
               
               
                   
               
               
                 5941 
                 ACGCCCCGAA CCTTGCATCA AGGCTCCTTG GTGTGGCCAC AGCAGACCAG ATGGGAAATT 
               
               
                   
               
               
                 6001 
                 ATTTGTGTTG AGTGGAAAAA AATCAGTTTT TGTAAAGATG TCAGTAACAT TCCACATCGT 
               
               
                   
               
               
                 6061 
                 CCTCCCTTTC TCTAAGAGGC CATCTCTAAG ATGTCAGATG TAGAGGAGAG AGAGCGAGAG 
               
               
                   
               
               
                 6121 
                 AACATCTTCC TTCTCTACCA TCACTCCTGT GGCGGTCACC ACCACCACCT CTCCCGCCCT 
               
               
                   
               
               
                 6181 
                 TACCAGCAGA AAGCAATGCA AACTGAGCTG CTTTAGTCCT TGAGAAATTG TGAAACAAAC 
               
               
                   
               
               
                 6241 
                 ACAAATATCA TAAAAGGAGC TGGTGATTCA GCTGGGTCCA GGTGAAGTGA CCTGCTGTTG 
               
               
                   
               
               
                 6301 
                 AGACCGGTAC AAATTGGATT TCAGGAAGGA GACTCCATCA CAGCCAGGAC CTTTCGTGCC 
               
               
                   
               
               
                 6361 
                 ATGGAGAGTG TTGGCCTCTT GTCTTTCTTC CCTGCTTTGC TGCTTTGCTC TCTGAAACCT 
               
               
                   
               
               
                 6421 
                 ACATTCCGTC AGTTTCCGAA TGCGAGGGCC TGGGATGAAT TTGGTGCCTT TCCATATCTC 
               
               
                   
               
               
                 6481 
                 GTTCTCTCTC CTTCCCCTGC GTTTCCTCTC CATCCTTCAT CCTCCATTGG TCCTTTTTTT 
               
               
                   
               
               
                 6541 
                 TTCTTTCATT TTTTATTTAA TTTCTTTTCT TCCTGTCTGT TCCTCCCCTA ATCCTCTATT 
               
               
                   
               
               
                 6601 
                 TTATTTTTAT TTTTTGTAAA GCCAAGTAGC TTTAAGATAA AGTGGTGGTC TTTTGGATGA 
               
               
                   
               
               
                 6661 
                 GGGAATAATG CATTTTTAAA TAAAATACCA ATATCAGGAA GCCATTTTTT ATTTCAGGAA 
               
               
                   
               
               
                 6721 
                 ATGTAAGAAA CCATTATTTC AGGTTATGAA AGTATAACCA AGCATCCTTT TGGGCAATTC 
               
               
                   
               
               
                 6781 
                 CTTACCAAAT GCAGAAGCTT TTCTGTTCGA TGCACTCTTT CCTCCTTGCC ACTTACCTTT 
               
               
                   
               
               
                 6841 
                 GCAAAGTTAA AAAAAAGGGG GGAGGGAATG GGAGAGAAAG CTGAGATTTC AGTTTCCTAC 
               
               
                   
               
               
                 6901 
                 TGCAGTTTCC TACCTGCAGA TCCAGGGGCT GCTGTTGCCT TTGGATGCCC CACTGAGGTC 
               
               
                   
               
               
                 6961 
                 CTAGAGTGCC TCCAGGGTGG TCTTCCTGTA GTCATAACAG CTAGCCAGTG CTCACCAGCT 
               
               
                   
               
               
                 7021 
                 TACCAGATTG CCAGGACTAA GCCATCCCAA AGCACAAGCA TTGTGTGTCT CTGTGACTGC 
               
               
                   
               
               
                 7081 
                 AGAGAAGAGA GAATTTTGCT TCTGTTTTGT GTTTAAAAAA CCAACACGGA AGCAGATGAT 
               
               
                   
               
               
                 7141 
                 CCCGAGAGAG AGGCCTCTAG CATGGGTGAC CCAGCCGACC TCAGGCCGGT TTCCGCACTG 
               
               
                   
               
               
                 7201 
                 CCACAACTTT GTTCAAAGTT GCCCCCAATT GGAACCTGCC ACTTGGCATT AGAGGGTCTT 
               
               
                   
               
               
                 7261 
                 TCATGGGGAG AGAAGGAGAC TGAATTACTC TAAGCAAAAT GTGAAAAGTA AGGAAATCAG 
               
               
                   
               
               
                 7321 
                 CCTTTCATCC CGGTCCTAAG TAACCGTCAG CCGAAGGTCT CGTGGAACAC AGGCAAACCC 
               
               
                   
               
               
                 7381 
                 GTGATTTTGG TGCTCCTTGT AACTCAGCCC TGCAAAGCAA AGTCCCATTG ATTTAAGTTG 
               
               
                   
               
               
                 7441 
                 TTTGCATTTG TACTGGCAAG GCAAAATATT TTTATTACCT TTTCTATTAC TTATTGTATG 
               
               
                   
               
               
                 7501 
                 AGCTTTTGTT GTTTACTTGG AGGTTTTGTC TTTTACTACA AGTTTGGAAC TATTTATTAT 
               
               
                   
               
               
                 7561 
                 TGCTTGGTAT TTGTGCTCTG TTTAAGAAAC AGGCACTTTT TTTTATTATG GATAAAATGT 
               
               
                   
               
               
                 7621 
                 TGAGATGACA GGAGGTCATT TCAATATGGC TTAGTAAAAT ATTTATTGTT CCTTTATTCT 
               
               
                   
               
               
                 7681 
                 CTGTACAAGA TTTTGGGCCT CTTTTTTTCC TTAATGTCAC AATGTTGAGT TCAGCATGTG 
               
               
                   
               
               
                 7741 
                 TCTGCCATTT CATTTGTACG CTTGTTCAAA ACCAAGTTTG TTCTGGTTTC AAGTTATAAA 
               
               
                   
               
               
                 7801 
                 AATAAATTGG ACATTTAACT TGATCTCCAA A