FIELD OF THE INVENTION  
       [0001]     The invention is in the fields of neurology and pharmacology. The invention generally relates to methods of evaluating neuropathic pain and to methods of evaluating biological activity of drugs or drug candidates for treating neuropathies.  
       BACKGROUND OF THE INVENTION  
       [0002]     Painful neuropathies are characterized by spontaneous and/or abnormal stimulus-evoked pain such as allodynia or hyperalgesia. Symptoms of neuropathic pain often include spontaneous cramping, burning, or shooting pain, or pain caused by normally innocuous stimuli. Neuropathic pain has a neurogenic origin, i.e., it is initiated or caused by a primary lesion or dysfunction in the peripheral or central nervous system (see, e.g., Merskey and Bogdik (1994) Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms, 2nd ed., Seattle: IASP Press). Neuropathic pain can occur as a result of nerve damage due to infectious agents (e.g., herpesviruses), metabolic diseases (e.g., diabetes), neurodegenerative diseases (e.g., multiple sclerosis), nerve injury (e.g., amputation or cancer-induced nerve compression), etc. Current pharmacologic and nonpharmacologic therapies for chronic neuropathic pain provide only partial relief and the outcomes vary widely in individual patients.  
         [0003]     Conditions affecting the peripheral nervous system create pathophysiologic changes such as loss of small sensory fibers and/or demyelination. Such changes can be histologically observed in the skin. Indeed, histological evaluation of skin biopsies has become an accepted method for assessing peripheral nerve status in patients with neuropathic pain or peripheral neuropathy (Griffin et al. (2001) Curr. Opin. Neurol., 14:655-659). This approach allows one to evaluate the progression of nerve damage in disease and regeneration/re-innervation with treatment. Counting criteria include epidermal nerve fiber density, the number of fibers crossing the dermal-epidermal junction, etc. Skin biopsies can be performed in multiple sites over time, so that a spatiotemporal profile of epidermal innervation can be assessed. However, histological analysis of skin biopsies is a laborious and time-consuming procedure.  
         [0004]     Therefore, there exists a need in the art to develop new methods for treatment and assessment of neuropathic pain and peripheral neuropathy.  
       SUMMARY OF THE INVENTION  
       [0005]     The present invention results from the realization that skin biopsy samples can be nonhistologically evaluated for expression of gene(s) that reflect the neuropathic pain status (“surrogate markers of neuropathic pain”). The expression of such genes can be measured in skin biopsy homogenates in a rapid and quantitative manner. If the expression of the gene(s) in skin punch biopsy samples correlates with the beneficial effect of the drug or drug candidate on neuropathic pain or peripheral neuropathy, then the read-out represents a surrogate marker of drug activity associated with the reduction in neuropathic pain and/or peripheral neuropathy (“surrogate marker of neurotrophic activity”). Furthermore, gene expression in skin punch biopsy samples can be used as a read-out of in vivo biological activity of a drug or drug candidate regardless of the neuropathic pain status (“biomarker of in vivo biological activity of a neurotrophic agent” or “biomarker of a neurotrophic agent” for short).  
         [0006]     In one aspect, the invention provides methods of identifying surrogate markers of neuropathic pain. The methods of identifying a surrogate marker of neuropathic pain include: 
        (a) obtaining a first skin biopsy sample under conditions of neuropathic pain;     (b) obtaining a second skin biopsy sample under conditions of substantially no neuropathic pain;     (c) preparing tissue extracts from the first and the second samples; and     (d) determining an amount of at least one nucleic acid or protein in the tissue extracts. 
 
 A difference between the amount of the nucleic acid or the protein in the first sample and the amount of the same nucleic acid or protein in the second sample indicates that the nucleic acid or the protein is a surrogate marker of neuropathic pain. 
       
 
         [0011]     In another aspect, the invention provides methods of evaluating the level of neuropathic pain using such surrogate markers. The methods of evaluating the level of neuropathic pain using surrogate markers of neuropathic pain include: 
        (a) obtaining a first skin biopsy sample under conditions of neuropathic pain;     (b) obtaining a second skin biopsy sample under conditions of substantially no neuropathic pain;     (c) preparing tissue extracts from the first and the second samples; and     (d) determining an amount of at least one nucleic acid or protein in the tissues, the nucleic acid or the protein being a surrogate marker of neuropathic pain. 
 
 A difference between the amount of the nucleic acid or the protein in the first sample and the amount of the same nucleic acid or protein in the second sample indicates the level of neuropathic pain. 
       
 
         [0016]     In another aspect, the invention provides methods of evaluating neurotrophic activity of a compound or composition, for example, in evaluating the effect of a compound of composition on the level of neuropathic pain. The methods include: 
        (a) administering the compound or composition to the mammal having neuropathic pain;     (b) obtaining at least one skin biopsy sample from the mammal;     (c) preparing a tissue extract from the skin biopsy sample; and     (d) determining an amount of at least of one surrogate marker of neuropathic pain that is nucleic acid or protein in the tissue extract. 
 
 A difference in the amount of the nucleic acid or protein determined in step (d) and the amount of the same nucleic acid or protein expressed in the absence of the compound or composition indicates the level of efficacy of the compound or composition on neuropathic pain. 
       
 
         [0021]     In another aspect, the invention provides methods of identifying biomarkers of in vivo biological activity of a neurotrophic agent and methods of evaluating in vivo biological activity of a neurotrophic agent using such biomarkers. The methods of identifying biomarkers of in vivo biological activity of a neurotrophic agent include: 
        (a) administering the agent to a mammal;     (b) obtaining at least one skin biopsy sample from the mammal;     (c) preparing a tissue extract from the skin biopsy sample; and     (d) determining an amount of at least one nucleic acid or protein in the tissue extract. 
 
 A difference in the amount of the nucleic acid or protein determined in step (d) and the amount of the same nucleic acid or protein expressed in the absence of the agent indicates that the nucleic acid or the protein is a biomarker of in vivo biological activity of the agent. 
       
 
         [0026]     In another aspect, the invention provides methods of evaluating in vivo biological activity of a neurotrophic agent using biomarkers of in vivo biological activity of such an agent. The methods of evaluating in vivo biological activity of a neurotrophic agent include: 
        (a) administering the agent to a mammal;     (b) obtaining at least one skin biopsy sample from the mammal;     (c) preparing a tissue extract from the skin biopsy sample; and     (d) determining an amount of at least one nucleic acid or protein in the tissue extract. 
 
 A difference in the amount of the nucleic acid or protein determined in step (d) and the amount of the same nucleic acid or protein expressed in the absence of the agent indicates that the agent is biologically active. 
       
 
         [0031]     In illustrative embodiments, the neurotrophic agent being evaluated is artemin (also known as neublastin or enovin), a member of the glial-cell-line-derived neurotrophic factor (GDNF) family.  
         [0032]     Exemplary nucleotide and/or amino acid sequences of human and rat surrogate markers of neuropathic pain, surrogated markers of neurotrophic activity and biomarkers of in vivo biological activity of neurotrophic agents are also provided (see Table 1).  
                                       TABLE 1                               Preferred                       Group No.   SEQ ID NOs:   SEQ ID NOs:   Category*   Type   Species   Table No.                   I    1-308    1-42   SMP   DNA   Rat   Table 2       II   309-470   309-333   SMP   Protein   Rat   Table 3       III   471-630   471-493   SMP   DNA   Human   Table 4       IV   631-790   631-653   SMP   Protein   Human   Table 5       V   791-897   791-814   SMN   DNA   Rat   Table 6       VI   898-962   898-914   SMN   Protein   Rat   Table 7       VII    963-1038   963-979   SMN   DNA   Human   Table 8       VIII   1039-1114   1039-1055   SMN   Protein   Human   Table 9       IX   1115-1163   1115-1120   BMN   DNA   Rat   Table 10       X   1164-1178   1164-1166   BMN   Protein   Rat   Table 11       XI   1179-1207   1179-1182   BMN   DNA   Human   Table 12       XII   1208-1236   1208-1211   BMN   Protein   Human   Table 13                 *SMP - surrogate marker of neuropathic pain; SMN - surrogate marker of neurotrophic activity; BMN - biomarker of a neurotrophic agent.             
 
         [0033]     Various embodiments of the invention are set forth in the following description or will be understood from the description.  
     
    
     BRIEF DESCRIPTION OF THE FIGURES  
       [0034]      FIG. 1  shows results of a TaqMan™ analysis of gene expression of rc_AA818804_at (SEQ ID NO:18 and SEQ ID NO:799) in the L4 dermatome of rats subjected to spinal nerve ligation injury (SNL) and treament with artemin. The gene is expressed at a low level before injury, at a higher level following injury, and at a near-normal level after injury and treatment with artemin.  
         [0035]      FIG. 2  shows results of a TaqMan™ analysis of gene expression of X14812_at (SEQ ID NO:37 and SEQ ID NO:813) in the L4 dermatome of rats subjected to SNL and treament with artemin. The gene is expressed at a low level before injury, at a higher level following injury, and at a near-normal level after injury and treatment with artemin.  
         [0036]      FIG. 3  shows results of a TaqMan™ analysis of gene expression of rc_AA818120_at (SEQ ID NO:31 and SEQ ID NO:808) in the L4 dermatome of rats subjected to SNL and treament with artemin. The gene is expressed at a low level before injury, at a higher level following injury, and at a near-normal level after injury and treatment with artemin.  
         [0037]      FIG. 4  shows results of a TaqMan™ analysis of gene expression of rc_AA946094_at (SEQ ID NO:2 and SEQ ID NO:791) in the L4 dermatome of rats subjected to SNL and treament with artemin. The gene is expressed at a low level before injury, at a higher level following injury, and at a near-normal level after injury and treatment with artemin.  
         [0038]      FIG. 5  shows results of a TaqMan™ analysis of gene expression of X07314cds_at (SEQ ID NO:11 and SEQ ID NO:796) in the L4 dermatome of rats subjected to SNL and treament with artemin. The gene is expressed at a low level before injury, at a higher level following injury, and at a near-normal level after injury and treatment with artemin.  
         [0039]      FIG. 6  shows results of a TaqMan™ analysis of expression of gene M27151_at (SEQ ID NO:22 and SEQ ID NO:801) in the L4 dermatome of rats subjected to SNL and treament with artemin. The gene is expressed at a low level before injury, at a higher level following injury, and at a near-normal level after injury and treatment with artemin.  
         [0040]      FIG. 7  shows results of an Affymatrix analysis of expression of gene rc_AI072712_at (SEQ ID NO:1118) in the L4 dermatome of rats subjected to SNL and treament with artemin. Regardsless of injury state, this gene is expressed at a relatively high level in the vehicle-treated samples, and at a much reduced level following treatment with artemin. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0041]     In the experiments leading to the present invention, rats were subjected to unilateral spinal nerve ligation (SNL) to induce unilateral neuropathic pain. Following SNL, some rats were systemically administered artemin, a neurotrophic factor shown to reduce neuropathic pain (Gardell et al. (2003) Nature Med., 9(11):1383-1389). The induced neuropathic pain was assessed using behavioral tests. Skin samples were then obtained bilaterally and tissue extracts were prepared. RNA from these tissue extracts was subjected to Affymetrix GeneChip™ expression analysis to determine gene expression profiles in various samples.  
         [0042]     The heterogeneity of tissues usually makes it difficult to detect small changes in transcription in tissue samples, especially if the changes are restricted to small subpopulations of cells or are a result of indirect effects. Despite this difficulty, the present invention is based, in part, on the discovery and demonstration that detectable changes in gene expression in skin biopsy homogenates reflect the neuropathic pain status.  
         [0043]     In particular, the methods of the invention may be used to identify genes whose expression levels correlate with neuropathic pain (surrogate markers of neuropathic pain). The invention may be also used to identify a subset of these genes whose expression levels are at least partially normalized by the artemin treatment (surrogate markers of neurotrophic activity). The invention may be used to identify an additional set of genes whose expression levels correlate with the presence of biologically active artemin regardless of the neuropathic pain status (biomarkers of a neurotrophic agent).  
         [0000]     Surrogate Markers of Neuropathic Pain  
         [0044]     The invention provides a method of identifying a surrogate marker of neuropathic pain in a mammal, comprising: 
        (a) obtaining a first skin biopsy sample under conditions of neuropathic pain;     (b) obtaining a second skin biopsy sample under conditions of substantially no neuropathic pain;     (c) preparing tissue extracts from the first and the second samples; and     (d) determining an amount of at least one nucleic acid or protein in the tissue extracts; 
 
 wherein a difference between the amount of the nucleic acid or the protein in the first sample and the amount of the same nucleic acid or protein in the second sample indicates that the nucleic acid or the protein is a surrogate marker of neuropathic pain. In some embodiments, the amount of the nucleic acid or the protein in the first sample will differ from the amount of the same nucleic acid or protein in the second sample by, for example, 2, 3, 4, 5, 8, 10, 20, 30, 40, 50, 80, 100-fold, or more. The difference (also referred to as “fold-change”) indicates a correlation of the downregulation or upregulation of the relevant gene and neuropathic pain. The greater the fold-change in expression and/or the higher the degree of correlation with neuropathic pain, the more preferable the nucleic acid or protein is as a surrogate marker of neuropathic pain. 
       
 
         [0049]     The first and the second samples can be obtained from the same mammal or from different mammals. For example, the first and second samples can be obtained from the same mammal from different regions of the skin, one region affected by neuropathic pain or peripheral neuropathy, and the other region not affected by pain or neuropathy. In another example, the first and second samples can be obtained from the same region of the skin in the same mammal but at different times. For example, a first sample can be collected prior to inducing neuropathic pain and the second sample is obtained following induction of neuropathic pain. In yet another example, the first sample can be collected from the region affected by neuropathic pain, and the second sample is obtained from the same region following treatment. Alternatively, the first and second samples can be obtained from different mammals and the amounts of a nucleic acid or protein are compared with reference to a common control using statistical analysis.  
         [0050]     Illustrative methods of identifying a surrogate marker of neuropathic pain in rats are provided in the Examples. 308 rat nucleic acids (Table 2) were identified following these illustrative methods. Corresponding protein sequences and human orthologues were then identified using publicly available databases such as GenBank™. 162 rat protein sequences (Table 3), 160 human nucleic acid sequences (Table 4), and 160 human protein sequences (Table 5) were identified in this manner.  
         [0051]     The invention provides a method of evaluating the level of neuropathic pain in a mammal, comprising: 
        (a) obtaining a first skin biopsy sample under conditions of neuropathic pain;     (b) obtaining a second skin biopsy sample under conditions of substantially no neuropathic pain;     (c) preparing tissue extracts from the first and the second samples; and     (d) determining an amount of at least one nucleic acid or protein in the tissues, the nucleic acid or the protein being a surrogate marker of neuropathic pain; 
 
 wherein a difference between the amount of the nucleic acid or the protein in the first sample and the amount of the same nucleic acid or protein in the second sample indicates the level of neuropathic pain. In some embodiments, the amount of the nucleic acid or the protein in the first sample will differ from the amount of the same nucleic acid or protein in the second sample by, for example, 2, 3, 4, 5, 8, 10, 20, 30, 40, 50, 80, 100-fold, or more. The difference (“fold-change”) in the expression levels of a relevant surrogate marker of neuropathic pain correlates with the level, or degree, or neuropathic pain. Generally, surrogate markers of neuropathic pain that exhibit greater fold-change values indicate a higher degree of neuropathic pain. 
       
 
         [0056]     The first and the second samples can be obtained from the same mammal or from different mammals as described herein.  
         [0057]     In some embodiments, the surrogate marker of neuropathic pain is a nucleic acid. In illustrative embodiments, the nucleic acid comprises a nonredundant subsequence of any one of the rat nucleotide sequences of SEQ ID NOs:1-308, preferably SEQ ID NOs:1-42. In other illustrative embodiments, a surrogate marker of neuropathic pain is a nucleic acid that comprises a nonredundant subsequence of any one of the human nucleotide sequences of SEQ ID NOs:471-630, preferably SEQ ID NOs:471-493.  
         [0058]     In some embodiments, the surrogate marker of neuropathic pain is a protein. In illustrative embodiments, the protein comprises a nonredundant subsequence of any one of the rat protein sequences of SEQ ID NOs:309-470, preferably SEQ ID NOs:309-333. In other illustrative embodiments, a surrogate marker of neuropathic pain is a protein that comprises a nonredundant subsequence of any one of the human protein sequences of SEQ ID NOs:631-790, preferably SEQ ID NOs:631-653.  
         [0059]     Conditions in which neuropathic pain may occur, and therefore may require assessment in the course of diagnosis or treatment, include but are not limited to: traumatic (including iatrogenic) nerve injury, ischemic neuropathy, nerve compression/entrapment, polyneuropathy (hereditary, metabolic, toxic, inflammatory; infectious, paraneoplastic, nutritional, in amyloidosis and vasculitis), plexus injury root compression, stump and phantom pain after amputation, herpes zoster/postherpetic neuralgia, trigeminal and glossopharyngeal neuralgia, cancer-related neuropathy (due to neural invasion of the tumor, surgical nerve damage, radiation-induced nerve damage, chemotherapy-induced neuropathy), stroke (infarct or hemorrhage), multiple sclerosis, spinal cord injury, syringomyelia/syringobulbia, epilepsy, and space-occupying lesions. Examples of specific disorders include diabetic neuropathy, sensory neuropathy of AIDS and antiretroviral toxic neuropathy, idiopathic small fiber neuropathy, leprosy, Fabry disease. Additionally, the method of assessing neuropathic pain may be used to assess induced neuropathic pain in experimental animals, e.g., SNL-induced neuropathic pain in rats as described in the Examples.  
         [0060]     Assessment of pain with the methods of the invention may be conducted in the course of pharmacological and/or nonpharmacological treatments. Nonpharmacological treatments of neuropathic pain include transcutaneous electrical nerve stimulation, spinal cord stimulation, motor cortex stimulation, deep brain stimulation, decompression, neuroma removal, neurotomy, glycerol injection, radiofrequency nerve/root lesion, dorsal root entry zone lesion, and cordotomy.  
         [0000]     Surrogate Markers of Neurotrophic Activity  
         [0061]     A subset of surrogate markers of neuropathic pain is expected to be normalized as a result of a treatment with a compound or a composition that reduces neuropathic pain.  
         [0062]     Accordingly, the invention provides a method of evaluating the effect of a compound or composition on the level of neuropathic pain in a mammal, comprising: 
        (a) administering the compound or composition to the mammal having neuropathic pain;     (b) obtaining at least one skin biopsy sample from the mammal;     (c) preparing a tissue extract from the skin biopsy sample; and     (d) determining an amount of at least one nucleic acid or protein in the tissue extract, the nucleic acid or the protein being a surrogate marker of neuropathic pain; 
 
 wherein a difference in the amount of the nucleic acid or protein determined in step (d) and the amount of the same nucleic acid or protein expressed in the absence of the compound or composition indicates the level of efficacy of the compound or composition on neuropathic pain. 
       
 
         [0067]     The amount of a nucleic acid or protein expressed in the absence of the compound or composition can be determined by any suitable method. In one method, the amount of the nucleic acid or protein in the test sample is compared to the amount of the same nucleic acid or protein in another sample obtained in the absence of the compound or composition from the same mammal or from different mammals. The control sample may be collected before, during, or after the analysis. In another method, the amount of the nucleic acid or protein in the test sample is compared to that of one or more internal references. An internal reference is a nucleic acid or a protein whose expression levels under given conditions are known. Most typically, the reference is a gene that remains relatively constant under various conditions such as a housekeeping gene, e.g., actin or GAPDH.  
         [0068]     In some embodiments, the amount determined in step (d) will differ from the amount of the same nucleic acid or protein expressed in the absence of the compound or composition by, for example, 2, 3, 4, 5, 8, 10, 20, 30, 40, 50, 80, 100-fold, or more. The “normalization” of the expression level of a relevant surrogate marker of neuropathic pain towards the baseline expression level as in normal conditions (substantially no neuropathic pain) indicates that the compound or composition reduces neuropathic pain. The difference in expression levels under conditions of neuropathic pain and upon “normalization” (“fold-change-back”) indicates the level of neurotrophic activity of the compound or composition being evaluated. Generally, the greater fold-change-back values indicate that the compound or composition is expected to exhibit greater efficacy in treating neuropathic pain. Although greater fold-change-back values are preferred, it is also preferred that a fold-change-back value for a particular surrogate marker of neuropathic pain does not substantially exceed a corresponding fold-change value for the marker.  
         [0069]     Illustrative methods of evaluating the effect of a compound or composition on the level of neuropathic pain in rats are provided in the Examples. 107 rat nucleic acids (Table 6) were identified following these methods. Corresponding protein sequences and human orthologues were then identified using publicly available databases such as GenBank™. 65 rat protein sequences (Table 7), 76 human nucleic acid sequences (Table 8); and 76 human protein sequences (Table 9) were identified in this manner.  
         [0070]     In some embodiments, the surrogate marker of neurotrophic activity is a nucleic acid. In illustrative embodiments, the nucleic acid comprises a nonredundant subsequence of any one of the rat nucleotide sequences of SEQ ID NOs:791-897, preferably SEQ ID NOs:791-814. In other illustrative embodiments, a surrogate marker of neurotrophic activity is a nucleic acid that comprises a nonredundant subsequence of any one of the human nucleotide sequences of SEQ ID NOs:963-1038, preferably SEQ ID NOs:963-979.  
         [0071]     In some embodiments, the surrogate marker of neurotrophic activity is a protein. In illustrative embodiments, the protein comprises a nonredundant subsequence of any one of the rat protein sequences of SEQ ID NOs:898-962, preferably SEQ ID NOs:898-914. In other illustrative embodiments, the surrogate marker of neurotrophic activity is a protein that comprises a nonredundant subsequence of any one of the human protein sequences of SEQ ID NOs:1039-1114, preferably SEQ ID NOs:1039-1055.  
         [0072]     In some embodiments, the compound or composition to be evaluated is or comprises a neurotrophic agent. “Neurotrophic agent” is a compound that has neurotrophic activity, i.e., it affects generation, survival, growth, or maintenance of normal physiological function of neurons. Neurotrophic activity can be evaluated/measured by one or more methods known in the art, for example: 
        (1) RET kinase receptor activation ELISA (KIRA) (Milbrandt et al. (1998) Neuron, 20:245; Sadick et al., 1996, Anal. Biochem., 1996. 235(2):207);     (2) choline acyteltransferease enzymatic assays (Leibrock et al. (1989) Nature, 341:149;     (3)  3 H-dopamine uptake assay with dopaminergic neurons (Lev-Fen et al. (1993) Science, 260:1130; or     (4) rat pheochromocytome cell line PC12 assays (Ernfors et al. (1991) Nature, 350:1756; Darling et al. (1984) Methods for preparation and assay of nerve growth factor”, Cell Culture Methods for Molecular and Cellular Biology, vol. 4 (eds. Barnes et al.), pp. 79-83, Alan R. Liss, New York; Bradshaw (1978) Ann Rev. Biochem, 47:191).        
 
         [0077]     In illustrative embodiments, the neurotrophic agent being evaluated is artemin. Other examples of neurotrophic agents include neurotrophic factors such as other members of the GDNF family (e.g., GDNF, neurturin, persephin), nerve growth factor (NG F), brain-derived neurotrophic factor (BDNF), neutrotrophin-3 (NT-3), leukocyte migration inhibitory factor (LIF), interleukin 6 (IL6), basic fibroblast growth factor (bFGF), midkine, neutrotrophin-4 (NT4), ciliary neurotrophic factor (CNTF), pleiotrophin, epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and insulin-like growth factor type 1 (IGF-1). Yet other examples of neurotrophic agents include agonists and antagonists of these neurotrophic factors or their respective receptors. Examples of agonist and/or antagonists include antibodies against a neurotrophic factor or their receptors and soluble forms of the receptors such as GFR-α (receptor for neurturin); RETα4 (receptor for persephin); GFRα3 (receptor for artemin), TrkA (receptor for NGF), TrkB (receptor for BDNF), TrkC (receptor for NT-3), gp130/LIFRβ (receptor for LIF), and gp130 (receptor for IL6).  
         [0078]     In some embodiments, the compound or composition to be evaluated is a drug or drug candidates for treating neuropathies and include neurotrophic agents as described herein. Examples of drugs that are currently used for the treatment of neuropathic pain, and therefore may be evaluated for neurotrophic activity, include antidepressants (amitriptyline, maprotiline, selective serotonin reuptake inhibitors), antiepileptics (gabapentin, carbamazepine, clonazepam, lamotrigine, topiramate, phenyloin), local anesthetics, mexiletine, baclofen, clonidine, ketamine, dextrorphan, tramadol, guanethidine, and opioids (morphine, methadone, ketobemidone, fentanyl).  
       Biomarkers of Neurotrophic Agents  
       [0079]     The invention provides a method of identifying a biomarker of biological activity of a “neurotrophic agent” (as described herein). The method comprises: 
        (a) administering the agent to a mammal;     (b) obtaining at least one skin biopsy sample from the mammal;     (c) preparing a tissue extract from the skin biopsy sample; and     (d) determining an amount of at least one nucleic acid or protein in the tissue extract; 
 
 wherein a difference in the amount of the nucleic acid or protein determined in step (d) and the amount of the same nucleic acid or protein expressed in the absence of the agent indicates that the nucleic acid or the protein is a biomarker of in vivo biological activity of the agent. In some embodiments, the amount determined in step (d) will differ from the amount of the same nucleic acid or protein expressed in the absence of the agent by, for example, 2, 3, 4, 5, 8, 10, 20, 30, 40, 50, 80, 100-fold, or more. The difference in the levels of expression that is attributed to the presence of biologically active neurotrophic agent is termed “biomarker-fold-change.” The greater the biomarker-fold-change value is, the more preferable the nucleic acid or protein is as a biomarker of biological activity of a neurotrophic agent. Some biomarkers (e.g., SEQ ID NO:1120 and SEQ ID NO:1126) may also represent surrogate markers of pain, i.e., they correlate with both neuropathic pain and the presence of a biologically active neurotrophic agent. Additionally, some of these biomarkers (e.g., SEQ ID NO:1120 and SEQ ID NO:1126) may also serve as surrogate markers of neurotrophic activity. 
       
 
         [0084]     The amount of the same nucleic acid or protein expressed in the absence of the compound or composition can be determined by any suitable method. The skin biopsy sample(s) can be obtained from the same mammal or from different mammals.  
         [0085]     Illustrative methods of identifying a biomarker of biological activity of a “neurotrophic agent” in rats are provided in the Examples below. 49 rat nucleic acids (Table 10) were identified following these methods. Corresponding protein sequences and human orthologues were then identified using publicly available databases such as GenBank™. 15 rat protein sequences (Table 11), 29 human nucleic acid sequences (Table 12); and 29 human protein sequences (Table 13) were identified in this manner.  
         [0086]     The invention provides a method of evaluating biological activity of a neurotrophic agent, comprising: 
        (a) administering the agent to a mammai;     (b) obtaining at least one skin biopsy sample from the mammal;     (c) preparing a tissue extract from the skin biopsy sample; and     (d) determining an amount of at least one nucleic acid or protein in the tissue extract; the nucleic acid or protein being a biomarker of the biological activity of the neurotrophic agent; 
 
 wherein a difference in the amount of the nucleic acid or protein determined in step (d) and the amount of the same nucleic acid or protein expressed in the absence of the agent indicates that the agent is biologically active. In some embodiments, the amount determined in step (d) will differ from the amount of the same nucleic acid or protein expressed in the absence of the agent by, for example, 2, 3, 4, 5, 8, 10, 20, 30, 40, 50, 80, 100-fold, or more. 
       
 
         [0091]     The amount of the same nucleic acid or protein expressed in the absence of the compound or composition can be determined by any suitable method. The skin biopsy sample(s) can be obtained from the same mammal or from different mammals.  
         [0092]     In illustrative embodiments, the neurotrophic agent being evaluated is artemin, a member of the GDNF family.  
         [0093]     In some embodiments, the biomarker of biological activity of a neurotrophic agent is a nucleic acid. In illustrative embodiments, the nucleic acid comprises a nonredundant subsequence of any one of the rat nucleotide sequences of SEQ ID NOs:1115-1163, preferably SEQ ID NOs:1115-1120. In other illustrative embodiments, a biomarker of biological activity of a neurotrophic agent is a nucleic acid that comprises a nonredundant subsequence of any one of the human nucleotide sequences of SEQ ID NOs:1179-1207, preferably SEQ ID NOs:1179-1182.  
         [0094]     In some embodiments, the biomarker of biological activity of a neurotrophic agent is a protein. In illustrative embodiments, the protein comprises a nonredundant subsequence of any one of the rat protein sequences of SEQ ID NOs:1164-1178, preferably SEQ ID NOs:1164-1166. In other illustrative embodiments, a biomarker of biological activity of a neurotrophic agent is a protein that comprises a nonredundant subsequence of any one of the human protein sequences of SEQ ID NOs:1208-1236, preferably SEQ ID NOs:1208-1211.  
         [0000]     General Methods  
         [0095]     Various methods for obtaining skin biopsies are available. The least invasive is removal of the epidermis by placing a suction capsule with over the skin for 30-90 min to develop the blister. The epidermis separates cleanly at the dermal-epidermal junction (Kennedy et al. (1999) Muscle Nerve, 98:323-329; U.S. Pat. No. 6,071,247). This approach is painless and occurs without bleeding because all of the blood vessels terminate beneath the epidermis in the dermal papillae. For these reasons it may be particularly safe on, for example, the feet of diabetic patients. Another approach is simple punch biopsy of the skin. This procedure is also well tolerated. If the biopsy diameter is restricted to 3 mm or less no suture is needed. The biopsy site heals by granulation and leaves a small circular scar that gradually resolves.  
         [0096]     Expression levels, at the RNA or at the protein level, can be determined using conventional methods. Expression levels are usually scaled and/or normalized per total amount of RNA or protein in the sample and/or a control, which is typically a housekeeping gene such actin or GAPDH). RNA levels may be determined by, e.g., quantitative PCR (e.g., TaqMan™ PCR or RT-PCR), Northern blotting, or any other method for determining RNA levels, e.g., as described in Sambrook et al. (eds.) Cloning: A Laboratory Manual, 2nd ed., Cold Spring Harbor Laboratory Press, 1989, or Lodie et al. (2002) Tissue Eng., 8(5):739-751), or as described in the Examples. Protein levels may be determined, .e.g., by using Western blotting, ELISA, enzymatic activity assays, or any other method for determining protein levels, e.g., as described in Current Protocols in Molecular Biology (Ausubel et al. (eds.) New York: John Wiley and Sons, 1998).  
         [0097]     One or more markers of the same or different type can be used in the in the methods of the invention. For example, 1, 2, 3, 4, 5 or more nucleic acids and/or 1, 2, 3, 4, 5 or more proteins can be used for a read-out for (a) neuropathic pain, (b) effect of a compound or composition on the level of neuropathic pain, and/or (c) evaluating biological activity of a neurotrophic agent.  
         [0098]     While representative procedures shown in the Examples are performed using rodents, a skilled artisan will recognize that such procedures can be successfully performed in other mammal and within parameters clinically feasible in human subjects. For example, skin biopsies can be obtained from human patients having neuropathic pain and then subjected to a similar analysis as described herein. For human samples, commercially or custom-made human gene arrays can be used (e.g., Affymatrix™ Human Genome sets U133, U133A, and U95).  
         [0099]     The term “nonredundant subsequence,” as used herein, refers to a subsequence which is unique to the sequence in which it occurs. In some embodiments, a nonredunant subsequence is at least, for example, 10, 15, 20, 30, 40, 50, 70, 100, 200, 300, 400, 500, 1000, or 1500 nucleotides long.  
         [0100]     All or some of the following sequences and their nonredundant subsequences can be excluded from certain embodiments: (a) rat DNA SMPs as set out in SEQ ID NOs: 8, 15, 100, 171, 199, 244; (b) rat protein SMPs as set out in SEQ ID NOs: 315, 318, 408, 420; (c) human DNA SMPs as set out in SEQ ID NOs: 476, 478, 568, 578; (d) human protein SMP sas set out in SEQ ID NOs: 636, 638, 728, 738; (e) rat DNA SMNs as set out in SEQ ID NOs: 798, 834; (f) rat protein SMN set out in SEQ ID NO:903; (g) human DNA SMN set out in SEQ ID NO:967; (h) human protein SMN as set out in SEQ ID NO:1043; and (i) sequences disclosed U.S. Patent Application Publication No. US2003/0216341.  
                                           TABLE 2                           Rat DNA SMPs            SEQ       Accession       ID NO:   AffyID ™   Number                    1   rc_AI639444_at   NM_057191*       2   rc_AA946094_at   NM_021588       3   rc_AA891522_f_at   NM_017240*       4   rc_AA799471_at   AA799471       5   rc_AI172339_at   NM_175844       6   U31816_s_at   U31816       7   M24393_at   NM_017115*       8   M98819mRNA_s_at   M98819       9   rc_AI010701_at   AI010701       10   rc_AI010736_at   AI010736       11   X07314cds_at   X07314*       12   rc_AI639444_g_at   NM_057191*       13   rc_AA799396_at   AA799396       14   rc_AI169831_at   AI169831       15   rc_AI012182_s_at   NM_033234       16   L04684_at   L04684       17   rc_AI171653_at   AI171653       18   rc_AA818804_at   AA818804       19   rc_AI044544_at   AI044544       20   M12098_s_at   NM_012604*       21   rc_AI073178_at   AI073178       22   M27151_at   NM_013172*       23   rc_AI227690_at   AI227690       24   rc_AI175100_at   AI175100       25   AF077338_at   NM_031813*       26   X74832cds_at   NM_024485*       27   rc_AI105049_at   AI105049       28   rc_AA866452_s_at   AA866452*       29   AA108284_at   NM_019292*       30   rc_AI104913_at   NM_013044*       31   rc_AA818120_at   AA818120       32   X59864mRNA_at   X59864       33   AF039832_g_at   NM_019334       34   X15939_i_at   NM_017240*       35   rc_AA851497_f_at   AA851497       36   rc_AA818845_at   AA818845       37   X14812_at   NM_012606*       38   rc_AA800206_at   AA800206*       39   X15939_r_at   NM_017240*       40   rc_AA901245_at   AA901245       41   X59864mRNA_g_at   X59864       42   rc_AA924417_f_at   NM_053395*       43   rc_AI170763_at   AI170763       44   rc_AI170764_at   AI170764       45   rc_AA818947_at   AA818947       46   X81193_at   NM_057144*       47   rc_AI170760_at   AI170760       48   X80130_cds i_at   X80130       49   rc_AA818952_at   AA818952       50   rc_AA819140_at   NM_019292*       51   rc_AI170696_at   NM_133583       52   rc_AI170687_at   AI170687       53   rc_AA998888_f_at   AA998888*       54   rc_AA819891_at   AA819891       55   rc_AA998685_f_at   AA998685*       56   rc_AA998374_f_at   AA998374       57   rc_AA849917_at   AA849917       58   rc_AA819868_at   AA819868       59   rc_AA849501_s_at   AA849501*       60   rc_AA819699_at   AA819699       61   rc_AA892801_at   NM_017245       62   rc_AA875288_at   AA875288       63   rc_AA891037_at   AA891037       64   rc_AA891903_at   AA891903       65   rc_AA891938_at   AA891938       66   rc_AA892287_at   AA892287       67   rc_AA892313_at   AA892313       68   rc_AI172259_at   AI172259       69   rc_AA892468_g_at   NM_138836       70   rc_AA859829_g_at   AA859829       71   rc_AA892860_g_at   AA892860       72   rc_AA892999_at   AA892999       73   rc_AA893195_at   AA893195       74   rc_AA893199_at   AA893199       75   rc_AA893307_at   AA893307       76   rc_AA894101_g_at   AA894101       77   rc_AA892468_at   NM_138836       78   rc_AI233870_at   AI233870       79   X96437mRNA_g_at   X96437       80   Y09453cds_at   NM_019255       81   Z78279_at   Z78279       82   rc_AI172054_at   AI172054       83   rc_AI172150_at   AI172150       84   rc_AI172171_at   AI172171       85   rc_AA875206_at   NM_053747       86   rc_AI172189_at   AI172189       87   rc_AA859931_g_at   AA859931       88   rc_AI233915_at   AI233915       89   rc_AI236229_at   AI236229       90   rc_AA849974_at   AA849974       91   rc_AA858869_at   AA858869       92   rc_AA858921_at   AA858921       93   rc_AA859335_at   NM_017147*       94   X90475cds_at   X90475*       95   rc_AI172183_at   AI172183       96   K03467_s_at   NM_012604*       97   H32169_at   H32169       98   H32451_at   H32451       99   J00692_at   J00692*       100   J01435cds#8_s_at   J01435       101   J01436cds_s_at   J01436       102   J04993_at   NM_017184*       103   L11694_at   NM_017033       104   K02423cds_s_at   NM_020104*       105   D38056_at   NM_053599       106   L00088exp_cds#2_at   NM_020104*       107   L00382cds_at   L00382*       108   L01702_at   NM_012763       109   L01793_at   NM_031043       110   L01793_g_at   NM_031043       111   rc_AA799773_g_at   AA799773       112   K02111_at   K02111*       113   AF052540_s_at   NM_017117       114   AA942808_at   AA942808       115   AB000216_at   NM_134403       116   AB009999_g_at   NM_031242       117   AF002281_at   NM_053650       118   AF008439_at   NM_013173       119   AF013144_at   NM_133578       120   E12625cds_at   NM_080886       121   AF037072_at   NM_019292*       122   D64046_at   NM_022185       123   AF061726_s_at   NM_017117*       124   AF077338_g_at   NM_031813*       125   AF080507_at   AF080507       126   AF086624_s_at   NM_022602       127   AF093536_at   NM_031810       128   D37920_at   NM_017136       129   L13606_at   L13606*       130   AF030089UTR#1_at   NM_021584       131   rc_AA800245_at   AA800245*       132   M83298_g_at   NM_053999       133   M83676_at   M83676       134   M84176_at   NM_176079*       135   M86621_at   NM_012919       136   M89945mRNA_g_at   M89945       137   rc_AA799571_at   AA799571       138   L08505_at   NM_019226       139   rc_AA800221_at   NM_053395*       140   M57263_at   NM_031659       141   rc_AA800637_at   AA800637       142   rc_AA817802_at   AA817802       143   rc_AA817929_at   AA817929       144   rc_AA817969_at   AA817969       145   rc_AA817975_at   NM_031355       146   rc_AA818745_at   AA818745       147   rc_AA799773_at   AA799773       148   M21759mRNA_at   M21759       149   L24897_s_at   L24897*       150   L27124_s_at   NM_012993       151   L28818cds_at   NM_022195       152   M10140_at   NM_012530*       153   M13100cds#2_s_at   M13100       154   M16112_at   NM_021739       155   M63122_at   NM_013091       156   M18330_at   NM_133307       157   M62752_at   NM_012660       158   M23995_g_at   NM_017272       159   M27434_s_at   NM_147214       160   M32397_at   NM_020072       161   M37941mRNA_s_at   NM_138876       162   M37942   M37942           exon#2-3_s_at       163   M55534mRNA_s_at   NM_012935       164   rc_AA818807_at   AA818807       165   M16112_g_at   NM_021739       166   rc_AI232024_f_at   NM_017239*       167   rc_AI180281_at   NM_175843       168   rc_AI180442_at   NM_031840       169   rc_AI227677_at   AI227677       170   rc_AI230247_s_at   NM_019192       171   rc_AI230319_at   NM_171992       172   rc_AI230596_at   AI230596       173   rc_AI639187_at   AI639187       174   rc_AI231572_at   AI231572       175   rc_AI178893_at   AI178893       176   rc_AI236301_at   AI236301       177   rc_AI237371_at   NM_031812       178   rc_AI237700_at   AI237700       179   rc_AI638960_at   AI638960       180   rc_AI638986_s_at   AI638986       181   rc_AI171376_at   NM_053395*       182   rc_AI231279_at   AI231279       183   rc_AI175328_at   AI175328       184   rc_AA945861_at   AA945861       185   rc_AI171774_at   AI171774*       186   rc_AI172006_at   NM_021666       187   rc_AI172423_at   NM_181368       188   rc_AI172597_at   AI172597       189   rc_AI175011_at   AI175011       190   rc_AI179243_at   NM_145775       191   rc_AI175258_at   AI175258       192   rc_AI178921_s_at   NM_013159       193   rc_AI175348_at   AI175348       194   rc_AI175507_at   AI175507       195   rc_AI175539_at   NM_022499*       196   rc_AI175935_at   NM_173101*       197   rc_AI176584_at   NM_012817       198   rc_AI178559_at   NM_012923       199   rc_AI639233_s_at   AI639233       200   rc_AI175045_at   AI175045       201   X70871_at   NM_012923       202   X52311_at   NM_054006       203   X53504cds_at   X53504       204   X53504cds_g_at   X53504       205   X56133_at   X56133*       206   X60351cds_s_at   NM_012935       207   X64401cds_s_at   NM_173144       208   rc_AI639178_at   AI639178       209   X70369_s_at   X70369       210   X04267_at   NM_012604*       211   X74835cds_at   NM_019298       212   X76489cds_g_at   X76489       213   X78848cds_f_at   NM_031509       214   X80130cds_f_at   X80130*       215   Z78279_g_at   Z78279       216   Z83869cds_at   NM_021699       217   X64827cds_s_at   NM_012786*       218   U20195_s_at   NM_017033       219   rc_AI639324_at   AI639324       220   rc_AI639410_i_at   AI639410       221   rc_AI639410_s_at   AI639410       222   rc_AI639465_f_at   NM_080903*       223   rc_AI639532_at   AI639532       224   rc_H33725_at   NM_138531       225   X15939_f_at   NM_017240*       226   S74265_s_at   NM_013066       227   X12554cds_s_at   NM_012812       228   U25651_at   NM_031715*       229   U30938_at   NM_013066       230   U40836mRNA_s_at   NM_012786       231   U50736_s_at   NM_013220       232   U84727_at   NM_022398       233   U96130_at   NM_031043       234   rc_AI171372_at   AI171372       235   S49760_at   NM_080787       236   rc_AI029057_at   AI029057       237   rc_AI010583_at   NM_133424       238   rc_AI010605_at   AI010605*       239   rc_AI010742_at   AI010742       240   rc_AI011563_s_at   AI011563       241   rc_AI011709_at   AI011709       242   rc_AI011855_at   AI011855       243   rc_AI070208_at   AI070208       244   rc_AI014135_g_at   AI014135       245   rc_AA996612_at   AA996612       246   rc_AI029152_at   AI029152       247   rc_AI030091_at   AI030091       248   rc_AI043640_at   AI043640       249   rc_AI044292_s_at   AI044292       250   rc_AI045097_at   AI045097       251   rc_AI171535_s_at   AI171535       252   rc_AI014132_at   AI014132       253   rc_AA946469_at   AA946469       254   rc_AA924500_at   AA924500       255   rc_AA925122_at   AA925122       256   rc_AA925342_at   AA925342       257   rc_AA925664_at   AA925664       258   rc_AA944401_at   AA944401       259   rc_AA944560_at   NM_153469       260   rc_AI010562_at   AI010562*       261   rc_AA946457_at   AA946457       262   rc_AA997341_at   NM_053326       263   rc_AA955927_at   AA955927       264   rc_AA957123_at   AA957123       265   rc_AA963167_at   AA963167       266   rc_AA963627_at   AA963627       267   rc_AA963742_at   AA963742       268   rc_AA964584_at   AA964584       269   rc_AI070399_at   AI070399       270   rc_AA946108_at   NM_173306       271   rc_AI168935_at   AI168935       272   rc_AI104924_f_at   NM_017239*       273   rc_AI059955_s_at   NM_053959       274   rc_AI112050_at   AI112050       275   rc_AI112084_at   AI112084       276   rc_AI113309_at   AI113309       277   rc_AI136540_at   AI136540*       278   rc_AA924428_at   AA924428       279   rc_AI145367_at   NM_053874       280   rc_AI104864_g_at   AI104864       281   rc_AI169265_at   AI169265       282   rc_AI170777_at   NM_024398       283   rc_AI170777_g_at   NM_024398       284   rc_AI170793_at   AI170793       285   rc_AI170894_at   AI170894       286   rc_AI170985_at   NM_020104*       287   rc_AI171098_at   AI171098*       288   rc_AI137958_at   AI137958       289   rc_AI103376_at   AI103376       290   rc_AI071299_at   NM_031135       291   rc_AI071328_at   AI071328       292   rc_AI071769_at   AI071769       293   rc_AI072166_at   AI072166       294   rc_AI101481_at   AI101481       295   rc_AI111401_s_at   AI111401       296   rc_AI102103_g_at   NM_031083       297   rc_AI103473_at   NM_021865       298   rc_AI103507_at   AI103507       299   rc_AI103920_f_at   NM_017239*       300   rc_AI104035_s_at   AI104035       301   rc_AI104326_at   AI104326       302   rc_AI104349_at   AI104349       303   rc_AI104354_at   AI104354       304   rc_AI102057_at   AI102057       305   rc_AI104567_g_at   AI104567*       306   rc_AA892861_at   AA892861       307   rc_AI179358_at   AI179358       308   AA799397_at   AA799397                 *Muscle-specific             
 
         [0101]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                   
               
               
                 Rat Protein SMPs 
               
             
          
           
               
                 SEQ 
                   
                   
                 Table 2 
               
               
                 ID 
                   
                 Accession 
                 SEQ 
               
               
                 NO: 
                 AffyID ™ 
                 Number 
                 ID NO: 
               
               
                   
               
             
          
           
               
                 309 
                 rc_AI639444_at 
                 Q9ER30* 
                 1 
               
               
                 310 
                 rc_AA946094_at 
                 Q9QZ76 
                 2 
               
               
                 311 
                 rc_AA891522_f_at 
                 P02564* 
                 3 
               
               
                 312 
                 rc_AI172339_at 
                 Q8K4K7 
                 5 
               
               
                 313 
                 U31816_s_at 
                 Q02485 
                 6 
               
               
                 314 
                 M24393_at 
                 P20428* 
                 7 
               
               
                 315 
                 M98819 
                 NP_620231 
                 8 
               
               
                   
                 mRNA_s_at 
               
               
                 316 
                 X07314cds_at 
                 P08733* 
                 11 
               
               
                 317 
                 rc_AI639444_g_at 
                 Q9ER30* 
                 12 
               
               
                 318 
                 rc_AI012182_s_at 
                 P02091 
                 15 
               
               
                 319 
                 L04684_at 
                 Q02485 
                 16 
               
               
                 320 
                 M12098_s_at 
                 Q9QZV8* 
                 20 
               
               
                 321 
                 M27151_at 
                 P19335* 
                 22 
               
               
                 322 
                 AF077338_at 
                 O88599* 
                 25 
               
               
                 323 
                 X74832cds_at 
                 P25108* 
                 26 
               
               
                 324 
                 rc_AA866452_s_at 
                 P03996* 
                 28 
               
               
                 325 
                 AA108284_at 
                 P14141* 
                 29 
               
               
                 326 
                 rc_AI104913_at 
                 P70567* 
                 30 
               
               
                 327 
                 X59864mRNA_at 
                 Q03668** 
                 32 
               
               
                 328 
                 AF039832_g_at 
                 Q9R0W1 
                 33 
               
               
                 329 
                 X15939_i_at 
                 P02564* 
                 34 
               
               
                 330 
                 X14812_at 
                 P16409* 
                 37 
               
               
                 331 
                 X15939_r_at 
                 P02564* 
                 39 
               
               
                 332 
                 X59864 
                 Q03668** 
                 41 
               
               
                   
                 mRNA_g_at 
               
               
                 333 
                 rc_AA924417_f_at 
                 Q925F0* 
                 42 
               
               
                 334 
                 X81193_at 
                 P50463* 
                 46 
               
               
                 335 
                 X80130cds_i_at 
                 P04270 
                 48 
               
               
                 336 
                 rc_AA819140_at 
                 P14141* 
                 50 
               
               
                 337 
                 rc_AI170696_at 
                 Q8VBU2 
                 51 
               
               
                 338 
                 rc_AA819891_at 
                 Q9R272 
                 54 
               
               
                 339 
                 rc_AA849501_s_at 
                 Q63518* 
                 59 
               
               
                 340 
                 rc_AA892801_at 
                 P05197 
                 61 
               
               
                 341 
                 rc_AA892468_g_at 
                 Q9ES87 
                 69 
               
               
                 342 
                 rc_AA892468_at 
                 Q9ES87 
                 77 
               
               
                 343 
                 Y09453cds_at 
                 P97707 
                 80 
               
               
                 344 
                 Z78279_at 
                 Q63079 
                 81 
               
               
                 345 
                 rc_AA875206_at 
                 Q9JJP9 
                 85 
               
               
                 346 
                 rc_AA858869_at 
                 AAO34127 
                 91 
               
               
                 347 
                 rc_AA859335_at 
                 P45592* 
                 93 
               
               
                 348 
                 X90475cds_at 
                 Q63518* 
                 94 
               
               
                 349 
                 K03467_s_at 
                 Q9QZV8* 
                 96 
               
               
                 350 
                 J00692_at 
                 P02568* 
                 99 
               
               
                 351 
                 J01436cds_s_at 
                 AAA99907 
                 101 
               
               
                 352 
                 J04993_at 
                 P13413* 
                 102 
               
               
                 353 
                 L11694_at 
                 P38652 
                 103 
               
               
                 354 
                 K02423cds_s_at 
                 NP_064489* 
                 104 
               
               
                 355 
                 D38056_at 
                 P97553 
                 105 
               
               
                 356 
                 L00088exp_cds# 
                 NP_064489* 
                 106 
               
               
                 357 
                 L00382cds_at 
                 AAA42289* 
                 107 
               
               
                 358 
                 L01702_at 
                 Q03348 
                 108 
               
               
                 359 
                 L01793_at 
                 O08730 
                 109 
               
               
                 360 
                 L01793_g_at 
                 O08730 
                 110 
               
               
                 361 
                 K02111_at 
                 P04462* 
                 112 
               
               
                 362 
                 AF052540_s_at 
                 P16259 
                 113 
               
               
                 363 
                 AB000216_at 
                 O08764 
                 115 
               
               
                 364 
                 AB009999_g_at 
                 O35052 
                 116 
               
               
                 365 
                 AF002281_at 
                 O70208 
                 117 
               
               
                 366 
                 AF008439_at 
                 O54902 
                 118 
               
               
                 367 
                 AF013144_at 
                 O54838 
                 119 
               
               
                 368 
                 E12625cds_at 
                 O35532 
                 120 
               
               
                 369 
                 AF037072_at 
                 P14141* 
                 121 
               
               
                 370 
                 D64046_at 
                 Q63788 
                 122 
               
               
                 371 
                 AF061726_s_at 
                 P16259* 
                 123 
               
               
                 372 
                 AF077338_g_at 
                 O88599* 
                 124 
               
               
                 373 
                 AF086624_s_at 
                 O70444 
                 126 
               
               
                 374 
                 AF093536_at 
                 O89117 
                 127 
               
               
                 375 
                 D37920_at 
                 P52020 
                 128 
               
               
                 376 
                 L13606_at 
                 Q07443* 
                 129 
               
               
                 377 
                 AF030089UTR#1_at 
                 Q9WVP7 
                 130 
               
               
                 378 
                 M83298_g_at 
                 P36876 
                 132 
               
               
                 379 
                 M83676_at 
                 P35284 
                 133 
               
               
                 380 
                 M84176_at 
                 NP_788268* 
                 134 
               
               
                 381 
                 M86621_at 
                 P54290 
                 135 
               
               
                 382 
                 M89945mRNA_g_at 
                 NP_114028 
                 136 
               
               
                 383 
                 L08505_at 
                 P38650 
                 138 
               
               
                 384 
                 rc_AA800221_at 
                 Q925F0* 
                 139 
               
               
                 385 
                 M57263_at 
                 P23606 
                 140 
               
               
                 386 
                 rc_AA817975_at 
                 Q9R1Z0 
                 145 
               
               
                 387 
                 M21759mRNA_at 
                 Q99053 
                 148 
               
               
                 388 
                 L24897_s_at 
                 Q63350* 
                 149 
               
               
                 389 
                 L27124_s_at 
                 25499 
                 150 
               
               
                 390 
                 L28818cds_at 
                 NP_071531 
                 151 
               
               
                 391 
                 M10140_at 
                 P00564* 
                 152 
               
               
                 392 
                 M16112_at 
                 Q63094 
                 154 
               
               
                 393 
                 M63122_at 
                 P22934 
                 155 
               
               
                 394 
                 M18330_at 
                 170538 
                 156 
               
               
                 395 
                 M62752_at 
                 P27706 
                 157 
               
               
                 396 
                 M23995_g_at 
                 P13601 
                 158 
               
               
                 397 
                 M27434_s_at 
                 P02761 
                 159 
               
               
                 398 
                 M32397_at 
                 P20646 
                 160 
               
               
                 399 
                 M37941mRNA_s_at 
                 P10759 
                 161 
               
               
                 400 
                 M37942exn#2-3 
                 NP_620231 
                 162 
               
               
                 401 
                 M55534mRNA_s_at 
                 P23928 
                 163 
               
               
                 402 
                 M16112_g_at 
                 Q63094 
                 165 
               
               
                 403 
                 rc_AI232024_f_at 
                 P02563* 
                 166 
               
               
                 404 
                 rc_AI180281_at 
                 O08623 
                 167 
               
               
                 405 
                 rc_AI180442_at 
                 P05369 
                 168 
               
               
                 406 
                 rc_AI227677_at 
                 Q62940 
                 169 
               
               
                 407 
                 rc_AI230247_s_at 
                 P25236 
                 170 
               
               
                 408 
                 rc_AI230319_at 
                 P39948 
                 171 
               
               
                 409 
                 rc_AI231572_at 
                 AAP29778 
                 174 
               
               
                 410 
                 rc_AI237371_at 
                 Q9QX82 
                 177 
               
               
                 411 
                 rc_AI171376_at 
                 Q925F0* 
                 181 
               
               
                 412 
                 rc_AI172006_at 
                 Q9QX75 
                 186 
               
               
                 413 
                 rc_AI172423_at 
                 AAP12535 
                 187 
               
               
                 414 
                 rc_AI179243_at 
                 Q63503 
                 190 
               
               
                 415 
                 rc_AI178921_s_at 
                 P35559 
                 192 
               
               
                 416 
                 rc_AI175539_at 
                 P02625* 
                 195 
               
               
                 417 
                 rc_AI175935_at 
                 Q63356* 
                 196 
               
               
                 418 
                 rc_AI176584_at 
                 P24594 
                 197 
               
               
                 419 
                 rc_AI178559_at 
                 P39950 
                 198 
               
               
                 420 
                 rc_AI639233_s_at 
                 Q01129 
                 199 
               
               
                 421 
                 X70871_at 
                 P39950 
                 201 
               
               
                 422 
                 X52311_at 
                 P18395 
                 202 
               
               
                 423 
                 X53504cds_at 
                 P23358 
                 203 
               
               
                 424 
                 X53504cds_g_at 
                 P23358 
                 204 
               
               
                 425 
                 X56133_at 
                 P15999* 
                 205 
               
               
                 426 
                 X60351cds_s_at 
                 P23928 
                 206 
               
               
                 427 
                 X64401cds_s_at 
                 P04800 
                 207 
               
               
                 428 
                 X70369_s_at 
                 P13941 
                 209 
               
               
                 429 
                 X04267_at 
                 Q9QZV8* 
                 210 
               
               
                 430 
                 X74835cds_at 
                 P25110 
                 211 
               
               
                 431 
                 X76489cds_g_at 
                 P40241 
                 212 
               
               
                 432 
                 X78848cds_f_at 
                 Q9JLX3 
                 213 
               
               
                 433 
                 X80130cds_f_at 
                 P04270* 
                 214 
               
               
                 434 
                 Z78279_g_at 
                 Q63079 
                 215 
               
               
                 435 
                 Z83869cds_at 
                 O08679 
                 216 
               
               
                 436 
                 X64827cds_s_at 
                 P16221* 
                 217 
               
               
                 437 
                 U20195_s_at 
                 P38652 
                 218 
               
               
                 438 
                 rc_AI639465_f_at 
                 Q91Z63* 
                 222 
               
               
                 439 
                 rc_H33725_at 
                 Q8R424 
                 224 
               
               
                 440 
                 X15939_f_at 
                 P02564* 
                 225 
               
               
                 441 
                 S74265_s_at 
                 P15146 
                 226 
               
               
                 442 
                 X12554cds_s_at 
                 P10817 
                 227 
               
               
                 443 
                 U25651_at 
                 P47858* 
                 228 
               
               
                 444 
                 U30938_at 
                 P15146 
                 229 
               
               
                 445 
                 U40836mRNA_s_at 
                 P16221 
                 230 
               
               
                 446 
                 U50736_s_at 
                 Q8R560 
                 231 
               
               
                 447 
                 U84727_at 
                 P97700 
                 232 
               
               
                 448 
                 U96130_at 
                 O08730 
                 233 
               
               
                 449 
                 S49760_at 
                 140866 
                 235 
               
               
                 450 
                 rc_AI010583_at 
                 Q8R4I6 
                 237 
               
               
                 451 
                 rc_AA996612_at 
                 Q9Z2J4 
                 245 
               
               
                 452 
                 rc_AA946469_at 
                 AAP29778 
                 253 
               
               
                 453 
                 rc_AA925664_at 
                 O08813 
                 257 
               
               
                 454 
                 rc_AA944560_at 
                 AAN15275 
                 259 
               
               
                 455 
                 rc_AI010562_at 
                 Q63350* 
                 260 
               
               
                 456 
                 rc_AA997341_at 
                 Q62920 
                 262 
               
               
                 457 
                 rc_AA946108_at 
                 P70570 
                 270 
               
               
                 458 
                 rc_AI104924_f_at 
                 P02563* 
                 272 
               
               
                 459 
                 rc_AI059955_s_at 
                 O08839 
                 273 
               
               
                 460 
                 rc_AI145367_at 
                 P52481 
                 279 
               
               
                 461 
                 rc_AI170777_at 
                 Q9ER34 
                 282 
               
               
                 462 
                 rc_AI170777_g_at 
                 Q9ER34 
                 283 
               
               
                 463 
                 rc_AI170985_at 
                 NP_064489* 
                 286 
               
               
                 464 
                 rc_AI171098_at 
                 Q63518* 
                 287 
               
               
                 465 
                 rc_AI071299_at 
                 O08876 
                 290 
               
               
                 466 
                 rc_AI111401_s_at 
                 O35217 
                 295 
               
               
                 467 
                 rc_AI102103_g_at 
                 O08561 
                 296 
               
               
                 468 
                 rc_AI103473_at 
                 Q925T0 
                 297 
               
               
                 469 
                 rc_AI103920_f_at 
                 P02563* 
                 299 
               
               
                 470 
                 rc_AI104567_g_at 
                 P03996* 
                 305 
               
               
                   
               
               
                   *Muscle-specific    
               
               
                   **SPTREMBL    
               
             
          
         
       
     
         [0102]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                   
               
               
                 Human DNA SMPs 
               
             
          
           
               
                 SEQ 
                   
                   
                 Table 2 
               
               
                 ID 
                   
                 Accession 
                 SEQ 
               
               
                 NO: 
                 AffyID ™ 
                 Number 
                 ID NO: 
               
               
                   
               
             
          
           
               
                 471 
                 rc_AI639444_at 
                 NM_006063.1* 
                 1 
               
               
                 472 
                 rc_AA946094_at 
                 NM_005368.1 
                 2 
               
               
                 473 
                 rc_AA891522_f_at 
                 NM_000257.1* 
                 3 
               
               
                 474 
                 rc_AA799471_at 
                 2330600 
                 4 
               
               
                 475 
                 M24393_at 
                 NM_002479.2* 
                 7 
               
               
                 476 
                 M98819mRNA_s_at 
                 NM_000036 
                 8 
               
               
                 477 
                 rc_AI639444_g_at 
                 NM_006063.1* 
                 12 
               
               
                 478 
                 rc_AI012182_s_at 
                 NM_000518.4 
                 15 
               
               
                 479 
                 L04684_at 
                 NM_000719 
                 16 
               
               
                 480 
                 rc_AA818804_at 
                 7022045 
                 18 
               
               
                 481 
                 M12098_s_at 
                 NM_002470.1* 
                 20 
               
               
                 482 
                 M27151_at 
                 NM_002469.1* 
                 22 
               
               
                 483 
                 AF077338_at 
                 NM_004997.1* 
                 25 
               
               
                 484 
                 X74832cds_at 
                 NM_000079.1* 
                 26 
               
               
                 485 
                 rc_AA866452_s_at 
                 BC009978* 
                 28 
               
               
                 486 
                 AA108284_at 
                 NM_005181.2* 
                 29 
               
               
                 487 
                 rc_AI104913_at 
                 NM_003275.1* 
                 30 
               
               
                 488 
                 rc_AA818120_at 
                 1943766 
                 31 
               
               
                 489 
                 AF039832_g_at 
                 NM_000325.3 
                 33 
               
               
                 490 
                 X15939_i_at 
                 NM_000257.1* 
                 34 
               
               
                 491 
                 X14812_at 
                 NM_000258.1* 
                 37 
               
               
                 492 
                 X15939_r_at 
                 NM_000257.1* 
                 39 
               
               
                 493 
                 rc_AA924417_f_at 
                 NM_014332.1* 
                 42 
               
               
                 494 
                 X81193_at 
                 NM_003476.1* 
                 46 
               
               
                 495 
                 X80130cds_i_at 
                 BC009978 
                 48 
               
               
                 496 
                 rc_AA819140_at 
                 NM_005181.2* 
                 50 
               
               
                 497 
                 rc_AI170696_at 
                 NM_016250.1 
                 51 
               
               
                 498 
                 rc_AA892801_at 
                 NM_001961.2 
                 61 
               
               
                 499 
                 rc_AA892287_at 
                 NM_018653 
                 66 
               
               
                 500 
                 rc_AA892313_at 
                 NM_003193 
                 67 
               
               
                 501 
                 rc_AA892468_g_at 
                 NM_002773.2 
                 69 
               
               
                 502 
                 rc_AA859829_g_at 
                 NM_005882 
                 70 
               
               
                 503 
                 rc_AA892468_at 
                 NM_002773.2 
                 77 
               
               
                 504 
                 X96437mRNA_g_at 
                 NM_002727 
                 79 
               
               
                 505 
                 Y09453cds_at 
                 NM_000727.2 
                 80 
               
               
                 506 
                 Z78279_at 
                 BC036531 
                 81 
               
               
                 507 
                 rc_AA875206_at 
                 222989_s_at 
                 85 
               
               
                 508 
                 rc_AA859931_g_at 
                 NM_024069 
                 87 
               
               
                 509 
                 rc_AA859335_at 
                 NM_005507.1* 
                 93 
               
               
                 510 
                 K03467_s_at 
                 NM_002470.1* 
                 96 
               
               
                 511 
                 H32169_at 
                 BC018256 
                 97 
               
               
                 512 
                 J00692_at 
                 NM_009606* 
                 99 
               
               
                 513 
                 J04993_at 
                 NM_003281.2* 
                 102 
               
               
                 514 
                 L11694_at 
                 NM_002633.2 
                 103 
               
               
                 515 
                 K02423cds_s_at 
                 NM_079420.1* 
                 104 
               
               
                 516 
                 D38056_at 
                 NM_004428.2 
                 105 
               
               
                 517 
                 L00088exp_cds#2_at 
                 NM_079420.1* 
                 106 
               
               
                 518 
                 L00382cds_at 
                 X06825* 
                 107 
               
               
                 519 
                 L01702_at 
                 NM_002836.2 
                 108 
               
               
                 520 
                 L01793_at 
                 NM_004130.2 
                 109 
               
               
                 521 
                 L01793_g_at 
                 NM_004130.2 
                 110 
               
               
                 522 
                 K02111_at 
                 NM_002470* 
                 112 
               
               
                 523 
                 AF052540_s_at 
                 NM_000070.2 
                 113 
               
               
                 524 
                 AB000216_at 
                 NM_145804.1 
                 115 
               
               
                 525 
                 AB009999_g_at 
                 NM_001263.2 
                 116 
               
               
                 526 
                 AF002281_at 
                 NM_014476.1 
                 117 
               
               
                 527 
                 AF008439_at 
                 NM_000617.1 
                 118 
               
               
                 528 
                 AF013144_at 
                 NM_004419.2 
                 119 
               
               
                 529 
                 E12625cds_at 
                 NM_006745.2 
                 120 
               
               
                 530 
                 AF037072_at 
                 NM_005181.2* 
                 121 
               
               
                 531 
                 D64046_at 
                 NM_005027.1 
                 122 
               
               
                 532 
                 AF061726_s_at 
                 NM_000070.2* 
                 123 
               
               
                 533 
                 AF077338_g_at 
                 NM_004997.1* 
                 124 
               
               
                 534 
                 AF093536_at 
                 BC047677 
                 127 
               
               
                 535 
                 D37920_at 
                 NM_003129.2 
                 128 
               
               
                 536 
                 L13606_at 
                 XM_028522* 
                 129 
               
               
                 537 
                 AF030089UTR#1_at 
                 NM_004734.1 
                 130 
               
               
                 538 
                 M83298_g_at 
                 NM_002717.2 
                 132 
               
               
                 539 
                 M83676_at 
                 5410327 
                 133 
               
               
                 540 
                 M84176_at 
                 NM_002478* 
                 134 
               
               
                 541 
                 M86621_at 
                 NM_000722.1 
                 135 
               
               
                 542 
                 M89945mRNA_g_at 
                 NM_004462 
                 136 
               
               
                 543 
                 rc_AA799571_at 
                 13491977 
                 137 
               
               
                 544 
                 L08505_at 
                 NM_001376.2 
                 138 
               
               
                 545 
                 rc_AA800221_at 
                 NM_014332.1* 
                 139 
               
               
                 546 
                 M57263_at 
                 NM_000359.1 
                 140 
               
               
                 547 
                 rc_AA817975_at 
                 NM_005662.3 
                 145 
               
               
                 548 
                 rc_AA818745_at 
                 29488 
                 146 
               
               
                 549 
                 M21759mRNA_at 
                 XM_048104 
                 148 
               
               
                 550 
                 L24897_s_at 
                 XM_028522* 
                 149 
               
               
                 551 
                 L27124_s_at 
                 NM_002525.1 
                 150 
               
               
                 552 
                 L28818cds_at 
                 BC046391 
                 151 
               
               
                 553 
                 M10140_at 
                 NM_001824.2* 
                 152 
               
               
                 554 
                 M16112_at 
                 NM_001220.3 
                 154 
               
               
                 555 
                 M63122_at 
                 NM_001065.2 
                 155 
               
               
                 556 
                 M18330_at 
                 NM_006254.2 
                 156 
               
               
                 557 
                 M62752_at 
                 NM_001958.2 
                 157 
               
               
                 558 
                 M23995_g_at 
                 NM_000692 
                 158 
               
               
                 559 
                 M32397_at 
                 NM_001099.2 
                 160 
               
               
                 560 
                 M37941mRNA_s_at 
                 NM_000036.1 
                 161 
               
               
                 561 
                 M37942exn#2-3_s_at 
                 NM_000036 
                 162 
               
               
                 562 
                 M55534mRNA_s_at 
                 NM_001885.1 
                 163 
               
               
                 563 
                 M16112_g_at 
                 NM_001220.3 
                 165 
               
               
                 564 
                 rc_AI232024_f_at 
                 NM_002471.1* 
                 166 
               
               
                 565 
                 rc_AI180442_at 
                 NM_002004.1 
                 168 
               
               
                 566 
                 rc_AI227677_at 
                 D42055.1 
                 169 
               
               
                 567 
                 rc_AI230247_s_at 
                 NM_005410.1 
                 170 
               
               
                 568 
                 rc_AI230319_at 
                 NM_001758.1 
                 171 
               
               
                 569 
                 rc_AI237371_at 
                 NM_006016.3 
                 177 
               
               
                 570 
                 rc_AI171376_at 
                 NM_014332.1* 
                 181 
               
               
                 571 
                 rc_AI172006_at 
                 NM_032467 
                 186 
               
               
                 572 
                 rc_AI179243_at 
                 NM_021724.1 
                 190 
               
               
                 573 
                 rc_AI178921_s_at 
                 NM_004969.1 
                 192 
               
               
                 574 
                 rc_AI175539_at 
                 NM_002854.1* 
                 195 
               
               
                 575 
                 rc_AI175935_at 
                 NM_004998.1* 
                 196 
               
               
                 576 
                 rc_AI176584_at 
                 NM_000599.1 
                 197 
               
               
                 577 
                 rc_AI178559_at 
                 NM_004060.2 
                 198 
               
               
                 578 
                 rc_AI639233_s_at 
                 NM_001920.2 
                 199 
               
               
                 579 
                 X70871_at 
                 NM_004060.2 
                 201 
               
               
                 580 
                 X52311_at 
                 NM_002524.2 
                 202 
               
               
                 581 
                 X56133_at 
                 NM_004046.3* 
                 205 
               
               
                 582 
                 X60351cds_s_at 
                 NM_001885.1 
                 206 
               
               
                 583 
                 X64401cds_s_at 
                 BC003642 
                 207 
               
               
                 584 
                 X70369_s_at 
                 NM_000090.2 
                 209 
               
               
                 585 
                 X04267_at 
                 NM_002470.1* 
                 210 
               
               
                 586 
                 X74835cds_at 
                 NM_000751.1 
                 211 
               
               
                 587 
                 X76489cds_g_at 
                 NM_001769.2 
                 212 
               
               
                 588 
                 X78848cds_f_at 
                 NM_000847.3 
                 213 
               
               
                 589 
                 X80130cds_f_at 
                 BC009978* 
                 214 
               
               
                 590 
                 Z78279_g_at 
                 BC036531 
                 215 
               
               
                 591 
                 Z83869cds_at 
                 NM_004954.2 
                 216 
               
               
                 592 
                 X64827cds_s_at 
                 J04823* 
                 217 
               
               
                 593 
                 U20195_s_at 
                 NM_002633.2 
                 218 
               
               
                 594 
                 rc_AI639324_at 
                 NM_030793 
                 219 
               
               
                 595 
                 rc_AI639465_f_at 
                 NM_032588.2* 
                 222 
               
               
                 596 
                 rc_H33725_at 
                 NM_006463.2 
                 224 
               
               
                 597 
                 X15939_f_at 
                 NM_000257.1* 
                 225 
               
               
                 598 
                 S74265_s_at 
                 NM_002374.2 
                 226 
               
               
                 599 
                 X12554cds_s_at 
                 NM_005205.2 
                 227 
               
               
                 600 
                 U25651_at 
                 NM_000289.2* 
                 228 
               
               
                 601 
                 U30938_at 
                 NM_002374.2 
                 229 
               
               
                 602 
                 U40836mRNA_s_at 
                 1311703 
                 230 
               
               
                 603 
                 U50736_s_at 
                 NM_014391.1 
                 231 
               
               
                 604 
                 U84727_at 
                 NM_003562.3 
                 232 
               
               
                 605 
                 U96130_at 
                 NM_004130.2 
                 233 
               
               
                 606 
                 S49760_at 
                 BC043292 
                 235 
               
               
                 607 
                 rc_AI010583_at 
                 NM_001104.1 
                 237 
               
               
                 608 
                 rc_AI011709_at 
                 35526 
                 241 
               
               
                 609 
                 rc_AA996612_at 
                 NM_144573.1 
                 245 
               
               
                 610 
                 rc_AA925122_at 
                 NM_000363 
                 255 
               
               
                 611 
                 rc_AA925664_at 
                 NM_001664 
                 257 
               
               
                 612 
                 rc_AA944560_at 
                 NM_007066.3 
                 259 
               
               
                 613 
                 rc_AA997341_at 
                 NM_006457.1 
                 262 
               
               
                 614 
                 rc_AA946108_at 
                 NM_173306 
                 270 
               
               
                 615 
                 rc_AI168935_at 
                 NM_018286 
                 271 
               
               
                 616 
                 rc_AI104924_f_at 
                 NM_002471.1* 
                 272 
               
               
                 617 
                 rc_AI059955_s_at 
                 NM_004305.2 
                 273 
               
               
                 618 
                 rc_AI145367_at 
                 NM_006366.1 
                 279 
               
               
                 619 
                 rc_AI170777_at 
                 NM_001098.1 
                 282 
               
               
                 620 
                 rc_AI170777_g_at 
                 NM_001098.1 
                 283 
               
               
                 621 
                 rc_AI170894_at 
                 NM_001122 
                 288 
               
               
                 622 
                 rc_AI170985_at 
                 NM_079420.1* 
                 300 
               
               
                 623 
                 rc_AI103376_at 
                 NM_018112 
                 282 
               
               
                 624 
                 rc_AI071299_at 
                 NM_005655.1 
                 235 
               
               
                 625 
                 rc_AI111401_s_at 
                 NM_004897.2 
                 289 
               
               
                 626 
                 rc_AI102103_g_at 
                 NM_002651.1 
                 278 
               
               
                 627 
                 rc_AI103473_at 
                 NM_018664.1 
                 237 
               
               
                 628 
                 rc_AI103920_f_at 
                 NM_002471.1* 
                 281 
               
               
                 629 
                 rc_AI104354_at 
                 NM_016599 
                 93 
               
               
                 630 
                 rc_AI104567_g_at 
                 BC009978* 
                 200 
               
               
                   
               
               
                   *Muscle-specific    
               
             
          
         
       
     
         [0103]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                   
               
               
                 Human Protein SMPs 
               
             
          
           
               
                 SEQ 
                   
                   
                 Table 2 
                 Table 4 
               
               
                 ID 
                   
                 Accession 
                 SEQ ID 
                 SEQ ID 
               
               
                 NO: 
                 AffyID ™ 
                 Number 
                 NO: 
                 NO: 
               
               
                   
               
             
          
           
               
                 631 
                 rc_AI639444_at 
                 AAH06534* 
                 1 
                 471 
               
               
                 632 
                 rc_AA946094_at 
                 P02144 
                 2 
                 472 
               
               
                 633 
                 rc_AA891522_f_at 
                 P12883* 
                 3 
                 473 
               
               
                 634 
                 rc_AA799471_at 
                 O15273 
                 4 
                 474 
               
               
                 635 
                 M24393_at 
                 P15173* 
                 7 
                 475 
               
               
                 636 
                 M98819mRNA_s_at 
                 NP_000027 
                 8 
                 476 
               
               
                 637 
                 rc_AI639444_g_at 
                 AAH06534* 
                 12 
                 477 
               
               
                 638 
                 rc_AI012182_s_at 
                 P02023 
                 15 
                 478 
               
               
                 639 
                 L04684_at 
                 NP_000710 
                 16 
                 479 
               
               
                 640 
                 rc_AA818804_at 
                 Q9NWB1 
                 18 
                 480 
               
               
                 641 
                 M12098_s_at 
                 P11055* 
                 20 
                 481 
               
               
                 642 
                 M27151_at 
                 AAH17834* 
                 22 
                 482 
               
               
                 643 
                 AF077338_at 
                 AAH44226* 
                 25 
                 483 
               
               
                 644 
                 X74832cds_at 
                 P02708* 
                 26 
                 484 
               
               
                 645 
                 rc_AA866452_s_at 
                 AAH009987* 
                 28 
                 485 
               
               
                 646 
                 AA108284_at 
                 P07451* 
                 29 
                 486 
               
               
                 647 
                 rc_AI104913_at 
                 P28289* 
                 30 
                 487 
               
               
                 648 
                 rc_AA818120_at 
                 O00631 
                 31 
                 488 
               
               
                 649 
                 AF039832_g_at 
                 Q99697 
                 33 
                 489 
               
               
                 650 
                 X15939_i_at 
                 P12883* 
                 34 
                 490 
               
               
                 651 
                 X14812_at 
                 AAH09790* 
                 37 
                 491 
               
               
                 652 
                 X15939_r_at 
                 P12883* 
                 39 
                 492 
               
               
                 653 
                 rc_AA924417_f_at 
                 Q9UHP9* 
                 42 
                 493 
               
               
                 654 
                 X81193_at 
                 P50461* 
                 46 
                 494 
               
               
                 655 
                 X80130cds_i_at 
                 AAH009987 
                 48 
                 495 
               
               
                 656 
                 rc_AA819140_at 
                 P07451* 
                 50 
                 496 
               
               
                 657 
                 rc_AI170696_at 
                 CAD62321 
                 51 
                 497 
               
               
                 658 
                 rc_AA892801_at 
                 P13639 
                 61 
                 498 
               
               
                 659 
                 rc_AA892287_at 
                 NP_061123.2 
                 66 
                 499 
               
               
                 660 
                 rc_AA892313_at 
                 NP_003184.1 
                 67 
                 500 
               
               
                 661 
                 rc_AA892468_g_at 
                 Q16651 
                 69 
                 501 
               
               
                 662 
                 rc_AA859829_g_at 
                 NP_005873.1 
                 70 
                 502 
               
               
                 663 
                 rc_AA892468_at 
                 Q16651 
                 77 
                 503 
               
               
                 664 
                 X96437mRNA_g_at 
                 AAH22313 
                 79 
                 504 
               
               
                 665 
                 Y09453cds_at 
                 Q06432 
                 80 
                 505 
               
               
                 666 
                 Z78279_at 
                 P02452 
                 81 
                 506 
               
               
                 667 
                 rc_AA875206_at 
                 NP_038466.2 
                 85 
                 507 
               
               
                 668 
                 rc_AA859931_g_at 
                 NP_076974.1 
                 87 
                 508 
               
               
                 669 
                 rc_AA859335_at 
                 P23528* 
                 93 
                 509 
               
               
                 670 
                 K03467_s_at 
                 P11055* 
                 96 
                 510 
               
               
                 671 
                 H32169_at 
                 NP_068733.1 
                 97 
                 511 
               
               
                 672 
                 J00692_at 
                 NP_033736* 
                 99 
                 512 
               
               
                 673 
                 J04993_at 
                 AAH12600* 
                 102 
                 513 
               
               
                 674 
                 L11694_at 
                 AAH19920 
                 103 
                 514 
               
               
                 675 
                 K02423cds_s_at 
                 AAH05318* 
                 104 
                 515 
               
               
                 676 
                 D38056_at 
                 P20827 
                 105 
                 516 
               
               
                 677 
                 L00088expanded_cds#2_at 
                 AAH05318* 
                 106 
                 517 
               
               
                 678 
                 L00382cds_at 
                 CAA29971* 
                 107 
                 518 
               
               
                 679 
                 L01702_at 
                 AAH27308 
                 108 
                 519 
               
               
                 680 
                 L01793_at 
                 P46976 
                 109 
                 520 
               
               
                 681 
                 L01793_g_at 
                 P46976 
                 110 
                 521 
               
               
                 682 
                 K02111_at 
                 NP_002461* 
                 112 
                 522 
               
               
                 683 
                 AF052540_s_at 
                 P20807 
                 113 
                 523 
               
               
                 684 
                 AB000216_at 
                 Q8N961 
                 115 
                 524 
               
               
                 685 
                 AB009999_g_at 
                 Q92903 
                 116 
                 525 
               
               
                 686 
                 AF002281_at 
                 O43590 
                 117 
                 526 
               
               
                 687 
                 AF008439_at 
                 BAB93467 
                 118 
                 527 
               
               
                 688 
                 AF013144_at 
                 Q16690 
                 119 
                 528 
               
               
                 689 
                 E12625cds_at 
                 Q15800 
                 120 
                 529 
               
               
                 690 
                 AF037072_at 
                 P07451* 
                 121 
                 530 
               
               
                 691 
                 D64046_at 
                 O00459 
                 122 
                 531 
               
               
                 692 
                 AF061726_s_at 
                 P20807* 
                 123 
                 532 
               
               
                 693 
                 AF077338_g_at 
                 AAH44226* 
                 124 
                 533 
               
               
                 694 
                 AF093536_at 
                 AAH47677 
                 127 
                 534 
               
               
                 695 
                 D37920_at 
                 Q14534 
                 128 
                 535 
               
               
                 696 
                 L13606_at 
                 XP_028522* 
                 129 
                 536 
               
               
                 697 
                 AF030089UTR#1_at 
                 O15075 
                 130 
                 537 
               
               
                 698 
                 M83298_g_at 
                 AAH41071 
                 132 
                 538 
               
               
                 699 
                 M83676_at 
                 O88386 
                 133 
                 539 
               
               
                 700 
                 M84176_at 
                 NP_002469* 
                 134 
                 540 
               
               
                 701 
                 M86621_at 
                 P54289 
                 135 
                 541 
               
               
                 702 
                 M89945mRNA_g_at 
                 NP_004453 
                 136 
                 542 
               
               
                 703 
                 rc_AA799571_at 
                 Q9BXS4 
                 137 
                 543 
               
               
                 704 
                 L08505_at 
                 BAA20783 
                 138 
                 544 
               
               
                 705 
                 rc_AA800221_at 
                 Q9UHP9* 
                 139 
                 545 
               
               
                 706 
                 M57263_at 
                 AAH34699 
                 140 
                 546 
               
               
                 707 
                 rc_AA817975_at 
                 Q9Y277 
                 145 
                 547 
               
               
                 708 
                 rc_AA818745_at 
                 Q01484 
                 146 
                 548 
               
               
                 709 
                 M21759mRNA_at 
                 XP_048104 
                 148 
                 549 
               
               
                 710 
                 L24897_s_at 
                 XP_028522* 
                 149 
                 550 
               
               
                 711 
                 L27124_s_at 
                 O43847 
                 150 
                 551 
               
               
                 712 
                 L28818cds_at 
                 AAH46391 
                 151 
                 552 
               
               
                 713 
                 M10140_at 
                 P06732* 
                 152 
                 553 
               
               
                 714 
                 M16112_at 
                 AAH19070 
                 154 
                 554 
               
               
                 715 
                 M63122_at 
                 P19438 
                 155 
                 555 
               
               
                 716 
                 M18330_at 
                 AAH43350 
                 156 
                 556 
               
               
                 717 
                 M62752_at 
                 Q05639 
                 157 
                 557 
               
               
                 718 
                 M23995_g_at 
                 NP_000683 
                 158 
                 558 
               
               
                 719 
                 M32397_at 
                 P15309 
                 160 
                 559 
               
               
                 720 
                 M37941mRNA_s_at 
                 P23109 
                 161 
                 560 
               
               
                 721 
                 M37942exon#2-3_s_at 
                 NP_000027 
                 162 
                 561 
               
               
                 722 
                 M55534mRNA_s_at 
                 P02511 
                 163 
                 562 
               
               
                 723 
                 M16112_g_at 
                 AAH19070 
                 165 
                 563 
               
               
                 724 
                 rc_AI232024_f_at 
                 O60661* 
                 166 
                 564 
               
               
                 725 
                 rc_AI180442_at 
                 P14324 
                 168 
                 565 
               
               
                 726 
                 rc_AI227677_at 
                 P46934 
                 169 
                 566 
               
               
                 727 
                 rc_AI230247_s_at 
                 P49908 
                 170 
                 567 
               
               
                 728 
                 rc_AI230319_at 
                 AAH23620 
                 171 
                 568 
               
               
                 729 
                 rc_AI237371_at 
                 O95413 
                 177 
                 569 
               
               
                 730 
                 rc_AI171376_at 
                 Q9UHP9* 
                 181 
                 570 
               
               
                 731 
                 rc_AI172006_at 
                 NP_115856 
                 186 
                 571 
               
               
                 732 
                 rc_AI179243_at 
                 AAA52334 
                 190 
                 572 
               
               
                 733 
                 rc_AI178921_s_at 
                 P14735 
                 192 
                 573 
               
               
                 734 
                 rc_AI175539_at 
                 P20472* 
                 195 
                 574 
               
               
                 735 
                 rc_AI175935_at 
                 Q12965* 
                 196 
                 575 
               
               
                 736 
                 rc_AI176584_at 
                 P24593 
                 197 
                 576 
               
               
                 737 
                 rc_AI178559_at 
                 P51959 
                 198 
                 577 
               
               
                 738 
                 rc_AI639233_s_at 
                 P07585 
                 199 
                 578 
               
               
                 739 
                 X70871_at 
                 P51959 
                 201 
                 579 
               
               
                 740 
                 X52311_at 
                 AAH32446 
                 202 
                 580 
               
               
                 741 
                 X56133_at 
                 P25705* 
                 205 
                 581 
               
               
                 742 
                 X60351cds_s_at 
                 P02511 
                 206 
                 582 
               
               
                 743 
                 X64401cds_s_at 
                 AAH03642 
                 207 
                 583 
               
               
                 744 
                 X70369_s_at 
                 AAB59383 
                 209 
                 584 
               
               
                 745 
                 X04267_at 
                 P11055* 
                 210 
                 585 
               
               
                 746 
                 X74835cds_at 
                 Q07001 
                 211 
                 586 
               
               
                 747 
                 X76489cds_g_at 
                 P21926 
                 212 
                 587 
               
               
                 748 
                 X78848cds_f_at 
                 Q16772 
                 213 
                 588 
               
               
                 749 
                 X80130cds_f_at 
                 AAH009987* 
                 214 
                 589 
               
               
                 750 
                 Z78279_g_at 
                 P02452 
                 215 
                 590 
               
               
                 751 
                 Z83869cds_at 
                 Q15449 
                 216 
                 591 
               
               
                 752 
                 X64827cds_s_at 
                 P10176* 
                 217 
                 592 
               
               
                 753 
                 U20195_s_at 
                 AAH19920 
                 218 
                 593 
               
               
                 754 
                 rc_AI639324_at 
                 NP_110420.1 
                 219 
                 594 
               
               
                 755 
                 rc_AI639465_f_at 
                 Q969Q1* 
                 222 
                 595 
               
               
                 756 
                 rc_H33725_at 
                 O95630 
                 224 
                 596 
               
               
                 757 
                 X15939_f_at 
                 P12883* 
                 225 
                 597 
               
               
                 758 
                 S74265_s_at 
                 P11137 
                 226 
                 598 
               
               
                 759 
                 X12554cds_s_at 
                 AAH29818 
                 227 
                 599 
               
               
                 760 
                 U25651_at 
                 AAH12799* 
                 228 
                 600 
               
               
                 761 
                 U30938_at 
                 P11137 
                 229 
                 601 
               
               
                 762 
                 U40836mRNA_s_at 
                 P10176 
                 230 
                 602 
               
               
                 763 
                 U50736_s_at 
                 Q15327 
                 231 
                 603 
               
               
                 764 
                 U84727_at 
                 Q02978 
                 232 
                 604 
               
               
                 765 
                 U96130_at 
                 P46976 
                 233 
                 605 
               
               
                 766 
                 S49760_at 
                 S12969 
                 235 
                 606 
               
               
                 767 
                 rc_AI010583_at 
                 Q08043 
                 237 
                 607 
               
               
                 768 
                 rc_AI011709_at 
                 Q15155 
                 241 
                 608 
               
               
                 769 
                 rc_AA996612_at 
                 Q96DL0 
                 245 
                 609 
               
               
                 770 
                 rc_AA925122_at 
                 TPHUCC 
                 255 
                 610 
               
               
                 771 
                 rc_AA925664_at 
                 A32342 
                 257 
                 611 
               
               
                 772 
                 rc_AA944560_at 
                 Q9Y2B9 
                 259 
                 612 
               
               
                 773 
                 rc_AA997341_at 
                 O60705 
                 262 
                 613 
               
               
                 774 
                 rc_AA946108_at 
                 A55347 
                 270 
                 614 
               
               
                 775 
                 rc_AI168935_at 
                 NP_060756.1 
                 271 
                 615 
               
               
                 776 
                 rc_AI104924_f_at 
                 O60661* 
                 272 
                 616 
               
               
                 777 
                 rc_AI059955_s_at 
                 CAD28496 
                 273 
                 617 
               
               
                 778 
                 rc_AI145367_at 
                 P40123 
                 279 
                 618 
               
               
                 779 
                 rc_AI170777_at 
                 Q8TAQ6 
                 282 
                 619 
               
               
                 780 
                 rc_AI170777_g_at 
                 Q8TAQ6 
                 283 
                 620 
               
               
                 781 
                 rc_AI170894_at 
                 NP_001113.1 
                 285 
                 621 
               
               
                 782 
                 rc_AI170985_at 
                 AAH05318* 
                 286 
                 622 
               
               
                 783 
                 rc_AI103376_at 
                 NP_060582.1 
                 289 
                 623 
               
               
                 784 
                 rc_AI071299_at 
                 O75411 
                 290 
                 624 
               
               
                 785 
                 rc_AI111401_s_at 
                 O95172 
                 295 
                 625 
               
               
                 786 
                 rc_AI102103_g_at 
                 O15096 
                 296 
                 626 
               
               
                 787 
                 rc_AI103473_at 
                 Q9NR55 
                 297 
                 627 
               
               
                 788 
                 rc_AI103920_f_at 
                 O60661* 
                 299 
                 628 
               
               
                 789 
                 rc_AI104354_at 
                 NP_057683.1 
                 303 
                 629 
               
               
                 790 
                 rc_AI104567_g_at 
                 AAH009987* 
                 305 
                 630 
               
               
                   
               
               
                   *Muscle-specific    
               
             
          
         
       
     
         [0104]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 6 
               
             
             
               
                   
               
               
                   
               
               
                 Rat DNA SMNs 
               
             
          
           
               
                 SEQ 
                   
                   
                 Table 2 
               
               
                 ID 
                   
                 Accession 
                 SEQ 
               
               
                 NO: 
                 AffyID ™ 
                 Number 
                 ID NO: 
               
               
                   
               
             
          
           
               
                 791 
                 rc_AA946094_at 
                 NM_021588 
                 2 
               
               
                 792 
                 rc_AA891522_f_at 
                 NM_017240* 
                 3 
               
               
                 793 
                 rc_AA799471_at 
                 AA799471 
                 4 
               
               
                 794 
                 rc_AI172339_at 
                 NM_175844 
                 5 
               
               
                 795 
                 M24393_at 
                 NM_017115* 
                 7 
               
               
                 796 
                 X07314cds_at 
                 X07314* 
                 11 
               
               
                 797 
                 rc_AA799396_at 
                 AA799396 
                 13 
               
               
                 798 
                 rc_AI012182_s_at 
                 NM_033234 
                 15 
               
               
                 799 
                 rc_AA818804_at 
                 AA818804 
                 18 
               
               
                 800 
                 M12098_s_at 
                 NM_012604* 
                 20 
               
               
                 801 
                 M27151_at 
                 NM_013172* 
                 22 
               
               
                 802 
                 rc_AI227690_at 
                 AI227690 
                 23 
               
               
                 803 
                 rc_AI175100_at 
                 AI175100 
                 24 
               
               
                 804 
                 AF077338_at 
                 NM_031813* 
                 25 
               
               
                 805 
                 X74832cds_at 
                 NM_024485* 
                 26 
               
               
                 806 
                 AA108284_at 
                 NM_019292* 
                 29 
               
               
                 807 
                 rc_AI104913_at 
                 NM_013044* 
                 30 
               
               
                 808 
                 rc_AA818120_at 
                 AA818120 
                 31 
               
               
                 809 
                 X59864mRNA_at 
                 X59864 
                 32 
               
               
                 810 
                 AF039832_g_at 
                 NM_019334 
                 33 
               
               
                 811 
                 X15939_i_at 
                 NM_017240* 
                 34 
               
               
                 812 
                 rc_AA851497_f_at 
                 AA851497 
                 35 
               
               
                 813 
                 X14812_at 
                 NM_012606* 
                 37 
               
               
                 814 
                 X15939_r_at 
                 NM_017240* 
                 39 
               
               
                 815 
                 rc_AI170696_at 
                 NM_133583 
                 51 
               
               
                 816 
                 rc_AA892801_at 
                 NM_017245 
                 61 
               
               
                 817 
                 rc_AA875288_at 
                 AA875288 
                 62 
               
               
                 818 
                 rc_AA891938_at 
                 AA891938 
                 65 
               
               
                 819 
                 rc_AA892287_at 
                 AA892287 
                 66 
               
               
                 820 
                 rc_AA892313_at 
                 AA892313 
                 67 
               
               
                 821 
                 rc_AA892468_g_at 
                 NM_138836 
                 69 
               
               
                 822 
                 rc_AA859829_g_at 
                 AA859829 
                 70 
               
               
                 823 
                 rc_AA892860_g_at 
                 AA892860 
                 71 
               
               
                 824 
                 rc_AA893307_at 
                 AA893307 
                 75 
               
               
                 825 
                 rc_AA894101 g_at 
                 AA894101 
                 76 
               
               
                 826 
                 Z78279_at 
                 Z78279 
                 81 
               
               
                 827 
                 rc_AI172054_at 
                 AI172054 
                 82 
               
               
                 828 
                 rc_AA875206_at 
                 NM_053747 
                 85 
               
               
                 829 
                 rc_AI172189_at 
                 AI172189 
                 86 
               
               
                 830 
                 rc_AA859931_g_at 
                 AA859931 
                 87 
               
               
                 831 
                 rc_AA858921_at 
                 AA858921 
                 92 
               
               
                 832 
                 rc_AA859335_at 
                 NM_017147* 
                 93 
               
               
                 833 
                 H32169_at 
                 H32169 
                 97 
               
               
                 834 
                 J01435cds#8_s_at 
                 J01435 
                 100 
               
               
                 835 
                 J01436cds_s_at 
                 J01436 
                 101 
               
               
                 836 
                 J04993_at 
                 NM_017184* 
                 102 
               
               
                 837 
                 L11694_at 
                 NM_017033 
                 103 
               
               
                 838 
                 D38056_at 
                 NM_053599 
                 105 
               
               
                 839 
                 L01702_at 
                 NM_012763 
                 108 
               
               
                 840 
                 AB009999_g_at 
                 NM_031242 
                 116 
               
               
                 841 
                 AF008439_at 
                 NM_013173 
                 118 
               
               
                 842 
                 AF037072_at 
                 NM_019292* 
                 121 
               
               
                 843 
                 D64046_at 
                 NM_022185 
                 122 
               
               
                 844 
                 AF077338_g_at 
                 NM_031813* 
                 124 
               
               
                 845 
                 AF080507_at 
                 AF080507 
                 125 
               
               
                 846 
                 D37920_at 
                 NM_017136 
                 128 
               
               
                 847 
                 M83298_g_at 
                 NM_053999 
                 132 
               
               
                 848 
                 M83676_at 
                 M83676 
                 133 
               
               
                 849 
                 rc_AA799571_at 
                 AA799571 
                 137 
               
               
                 850 
                 M57263_at 
                 NM_031659 
                 140 
               
               
                 851 
                 rc_AA817975_at 
                 NM_031355 
                 145 
               
               
                 852 
                 rc_AA818745_at 
                 AA818745 
                 146 
               
               
                 853 
                 L27124_s_at 
                 NM_012993 
                 150 
               
               
                 854 
                 M18330_at 
                 NM_133307 
                 156 
               
               
                 855 
                 M32397_at 
                 NM_020072 
                 160 
               
               
                 856 
                 rc_AI227677_at 
                 AI227677 
                 169 
               
               
                 857 
                 rc_AI230247_s_at 
                 NM_019192 
                 170 
               
               
                 858 
                 rc_AI230596_at 
                 AI230596 
                 172 
               
               
                 859 
                 rc_AI638960_at 
                 AI638960 
                 179 
               
               
                 860 
                 rc_AI171376_at 
                 NM_053395* 
                 181 
               
               
                 861 
                 rc_AI172423_at 
                 NM_181368 
                 187 
               
               
                 862 
                 rc_AI178921_s_at 
                 NM_013159 
                 192 
               
               
                 863 
                 rc_AI175935_at 
                 NM_173101* 
                 196 
               
               
                 864 
                 rc_AI176584_at 
                 NM_012817 
                 197 
               
               
                 865 
                 X52311_at 
                 NM_054006 
                 202 
               
               
                 866 
                 X53504cds_g_at 
                 X53504 
                 204 
               
               
                 867 
                 X64401cds_s_at 
                 NM_173144 
                 207 
               
               
                 868 
                 X76489cds_g_at 
                 X76489 
                 212 
               
               
                 869 
                 Z78279_g_at 
                 Z78279 
                 215 
               
               
                 870 
                 Z83869cds_at 
                 NM_021699 
                 216 
               
               
                 871 
                 X64827cds_s_at 
                 NM_012786* 
                 217 
               
               
                 872 
                 rc_AI639324_at 
                 AI639324 
                 219 
               
               
                 873 
                 rc_AI639410_i_at 
                 AI639410 
                 220 
               
               
                 874 
                 rc_AI639465_f_at 
                 NM_080903* 
                 222 
               
               
                 875 
                 rc_H33725_at 
                 NM_138531 
                 224 
               
               
                 876 
                 X12554cds_s_at 
                 NM_012812 
                 227 
               
               
                 877 
                 U30938_at 
                 NM_013066 
                 229 
               
               
                 878 
                 U40836mRNA_s_at 
                 NM_012786 
                 230 
               
               
                 879 
                 S49760_at 
                 NM_080787 
                 235 
               
               
                 880 
                 rc_AI011709_at 
                 AI011709 
                 241 
               
               
                 881 
                 rc_AI043640_at 
                 AI043640 
                 248 
               
               
                 882 
                 rc_AI044292_s_at 
                 AI044292 
                 249 
               
               
                 883 
                 rc_AA925122_at 
                 AA925122 
                 255 
               
               
                 884 
                 rc_AA925664_at 
                 AA925664 
                 257 
               
               
                 885 
                 rc_AA946108_at 
                 NM_173306 
                 270 
               
               
                 886 
                 rc_AI168935_at 
                 AI168935 
                 271 
               
               
                 887 
                 rc_AA924428_at 
                 AA924428 
                 278 
               
               
                 888 
                 rc_AI170894_at 
                 AI170894 
                 285 
               
               
                 889 
                 rc_AI103376_at 
                 AI103376 
                 289 
               
               
                 890 
                 rc_AI071299_at 
                 NM_031135 
                 290 
               
               
                 891 
                 rc_AI072166_at 
                 AI072166 
                 293 
               
               
                 892 
                 rc_AI111401_s_at 
                 AI111401 
                 295 
               
               
                 893 
                 rc_AI103507_at 
                 AI103507 
                 298 
               
               
                 894 
                 rc_AI104349_at 
                 AI104349 
                 302 
               
               
                 895 
                 rc_AI104354_at 
                 AI104354 
                 303 
               
               
                 896 
                 rc_AA892861_at 
                 AA892861 
                 306 
               
               
                 897 
                 rc_AI179358_at 
                 AI179358 
                 307 
               
               
                   
               
               
                   *Muscle-specific    
               
             
          
         
       
     
         [0105]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 7 
               
             
             
               
                   
               
               
                   
               
               
                 Rat Protein SMPs 
               
             
          
           
               
                 SEQ 
                   
                   
                   
                   
               
               
                 ID 
                   
                 Accession 
                 Table 6 
                 Table 3 
               
               
                 NO: 
                 AffyID ™ 
                 Number 
                 SEQ ID NO: 
                 SEQ ID NO: 
               
               
                   
               
             
          
           
               
                 898 
                 rc_AA946094_at 
                 Q9QZ76 
                 2 
                 791 
               
               
                 899 
                 rc_AA891522_f_at 
                 P02564* 
                 3 
                 792 
               
               
                 900 
                 rc_AI172339_at 
                 Q8K4K7 
                 5 
                 794 
               
               
                 901 
                 M24393_at 
                 P20428* 
                 7 
                 795 
               
               
                 902 
                 X07314cds_at 
                 P08733* 
                 11 
                 796 
               
               
                 903 
                 rc_AI012182_s_at 
                 P02091 
                 15 
                 798 
               
               
                 904 
                 M12098_s_at 
                 Q9QZV8* 
                 20 
                 800 
               
               
                 905 
                 M27151_at 
                 P19335* 
                 22 
                 801 
               
               
                 906 
                 AF077338_at 
                 O88599* 
                 25 
                 804 
               
               
                 907 
                 X74832cds_at 
                 P25108* 
                 26 
                 805 
               
               
                 908 
                 AA108284_at 
                 P14141* 
                 29 
                 806 
               
               
                 909 
                 rc_AI104913_at 
                 P70567* 
                 30 
                 807 
               
               
                 910 
                 X59864mRNA_at 
                 Q03668** 
                 32 
                 809 
               
               
                 911 
                 AF039832_g_at 
                 Q9R0W1 
                 33 
                 810 
               
               
                 912 
                 X15939_i_at 
                 P02564* 
                 34 
                 811 
               
               
                 913 
                 X14812_at 
                 P16409* 
                 37 
                 813 
               
               
                 914 
                 X15939_r_at 
                 P02564* 
                 39 
                 814 
               
               
                 915 
                 rc_AI170696_at 
                 Q8VBU2 
                 51 
                 815 
               
               
                 916 
                 rc_AA892801_at 
                 P05197 
                 61 
                 816 
               
               
                 917 
                 rc_AA892468_g_at 
                 Q9ES87 
                 69 
                 821 
               
               
                 918 
                 Z78279_at 
                 Q63079 
                 81 
                 826 
               
               
                 919 
                 rc_AA875206_at 
                 Q9JJP9 
                 85 
                 828 
               
               
                 920 
                 rc_AA859335_at 
                 P45592* 
                 93 
                 832 
               
               
                 921 
                 J01436cds_s_at 
                 AAA99907 
                 101 
                 835 
               
               
                 922 
                 J04993_at 
                 P13413* 
                 102 
                 836 
               
               
                 923 
                 L11694_at 
                 P38652 
                 103 
                 837 
               
               
                 924 
                 D38056_at 
                 P97553 
                 105 
                 838 
               
               
                 925 
                 L01702_at 
                 Q03348 
                 108 
                 839 
               
               
                 926 
                 AB009999_g_at 
                 O35052 
                 116 
                 840 
               
               
                 927 
                 AF008439_at 
                 O54902 
                 118 
                 841 
               
               
                 928 
                 AF037072_at 
                 P14141* 
                 121 
                 842 
               
               
                 929 
                 D64046_at 
                 Q63788 
                 122 
                 843 
               
               
                 930 
                 AF077338_g_at 
                 O88599* 
                 124 
                 844 
               
               
                 931 
                 D37920_at 
                 P52020 
                 128 
                 846 
               
               
                 932 
                 M83298_g_at 
                 P36876 
                 132 
                 847 
               
               
                 933 
                 M83676_at 
                 P35284 
                 133 
                 848 
               
               
                 934 
                 M57263_at 
                 P23606 
                 140 
                 850 
               
               
                 935 
                 rc_AA817975_at 
                 Q9R1Z0 
                 145 
                 851 
               
               
                 936 
                 L27124_s_at 
                 25499 
                 150 
                 853 
               
               
                 937 
                 M18330_at 
                 170538 
                 156 
                 854 
               
               
                 938 
                 M32397_at 
                 P20646 
                 160 
                 855 
               
               
                 939 
                 rc_AI227677_at 
                 Q62940 
                 169 
                 856 
               
               
                 940 
                 rc_AI230247_s_at 
                 P25236 
                 170 
                 857 
               
               
                 941 
                 rc_AI171376_at 
                 Q925F0* 
                 181 
                 860 
               
               
                 942 
                 rc_AI172423_at 
                 AAP12535 
                 187 
                 861 
               
               
                 943 
                 rc_AI178921_s_at 
                 P35559 
                 192 
                 862 
               
               
                 944 
                 rc_AI175935_at 
                 Q63356* 
                 196 
                 863 
               
               
                 945 
                 rc_AI176584_at 
                 P24594 
                 197 
                 864 
               
               
                 946 
                 X52311_at 
                 P18395 
                 202 
                 865 
               
               
                 947 
                 X53504cds_g_at 
                 P23358 
                 204 
                 866 
               
               
                 948 
                 X64401cds_s_at 
                 P04800 
                 207 
                 867 
               
               
                 949 
                 X76489cds_g_at 
                 P40241 
                 212 
                 868 
               
               
                 950 
                 Z78279_g_at 
                 Q63079 
                 215 
                 869 
               
               
                 951 
                 Z83869cds_at 
                 O08679 
                 216 
                 870 
               
               
                 952 
                 X64827cds_s_at 
                 P16221* 
                 217 
                 871 
               
               
                 953 
                 rc_AI639465_f_at 
                 Q91Z63* 
                 222 
                 874 
               
               
                 954 
                 rc_H33725_at 
                 Q8R424 
                 224 
                 875 
               
               
                 955 
                 X12554cds_s_at 
                 P10817 
                 227 
                 876 
               
               
                 956 
                 U30938_at 
                 P15146 
                 229 
                 877 
               
               
                 957 
                 U40836mRNA_s_at 
                 P16221 
                 230 
                 878 
               
               
                 958 
                 S49760_at 
                 140866 
                 235 
                 879 
               
               
                 959 
                 rc_AA925664_at 
                 O08813 
                 257 
                 884 
               
               
                 960 
                 rc_AA946108_at 
                 P70570 
                 270 
                 885 
               
               
                 961 
                 rc_AI071299_at 
                 O08876 
                 290 
                 890 
               
               
                 962 
                 rc_AI111401_s_at 
                 O35217 
                 295 
                 892 
               
               
                   
               
               
                   *Muscle-specific    
               
               
                   **SPTREMBL    
               
             
          
         
       
     
         [0106]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 8 
               
             
             
               
                   
               
               
                   
               
               
                 Human DNA SMNs 
               
             
          
           
               
                   
                   
                   
                 Table 6 
                 Table 4 
               
               
                 SEQ ID 
                   
                   
                 SEQ ID 
                 SEQ ID 
               
               
                 NO: 
                 AffyID ™ 
                 Accession Number 
                 NO: 
                 NO: 
               
               
                   
               
             
          
           
               
                 963 
                 rc_AA946094_at 
                 NM_005368.1 
                 2 
                 791 
               
               
                 964 
                 rc_AA891522_f_at 
                 NM_000257.1* 
                 3 
                 792 
               
               
                 965 
                 rc_AA799471_at 
                 2330600 
                 4 
                 793 
               
               
                 966 
                 M24393_at 
                 NM_002479.2* 
                 7 
                 795 
               
               
                 967 
                 rc_AI012182_s_at 
                 NM_000518.4 
                 15 
                 798 
               
               
                 968 
                 rc_AA818804_at 
                 7022045 
                 18 
                 799 
               
               
                 969 
                 M12098_s_at 
                 NM_002470.1* 
                 20 
                 800 
               
               
                 970 
                 M27151_at 
                 NM_002469.1* 
                 22 
                 801 
               
               
                 971 
                 AF077338_at 
                 NM_004997.1* 
                 25 
                 804 
               
               
                 972 
                 X74832cds_at 
                 NM_000079.1* 
                 26 
                 805 
               
               
                 973 
                 AA108284_at 
                 NM_005181.2* 
                 29 
                 806 
               
               
                 974 
                 rc_AI104913_at 
                 NM_003275.1* 
                 30 
                 807 
               
               
                 975 
                 rc_AA818120_at 
                 1943766 
                 31 
                 808 
               
               
                 976 
                 AF039832_g_at 
                 NM_000325.3 
                 33 
                 810 
               
               
                 977 
                 X15939_i_at 
                 NM_000257.1* 
                 34 
                 811 
               
               
                 978 
                 X14812_at 
                 NM_000258.1* 
                 37 
                 813 
               
               
                 979 
                 X15939_r_at 
                 NM_000257.1* 
                 39 
                 814 
               
               
                 980 
                 rc_AI170696_at 
                 NM_016250.1 
                 51 
                 815 
               
               
                 981 
                 rc_AA892801_at 
                 NM_001961.2 
                 61 
                 816 
               
               
                 982 
                 rc_AA892287_at 
                 NM_018653 
                 66 
                 819 
               
               
                 983 
                 rc_AA892313_at 
                 NM_003193 
                 67 
                 820 
               
               
                 984 
                 rc_AA892468_g_at 
                 NM_002773.2 
                 69 
                 821 
               
               
                 985 
                 rc_AA859829_g_at 
                 NM_005882 
                 70 
                 822 
               
               
                 986 
                 Z78279_at 
                 BC036531 
                 81 
                 826 
               
               
                 987 
                 rc_AA875206_at 
                 222989_s_at 
                 85 
                 828 
               
               
                 988 
                 rc_AA859931_g_at 
                 NM_024069 
                 87 
                 830 
               
               
                 989 
                 rc_AA859335_at 
                 NM_005507.1* 
                 93 
                 832 
               
               
                 990 
                 H32169_at 
                 BC018256 
                 97 
                 833 
               
               
                 991 
                 J04993_at 
                 NM_003281.2* 
                 102 
                 836 
               
               
                 992 
                 L11694_at 
                 NM_002633.2 
                 103 
                 837 
               
               
                 993 
                 D38056_at 
                 NM_004428.2 
                 105 
                 838 
               
               
                 994 
                 L01702_at 
                 NM_002836.2 
                 108 
                 839 
               
               
                 995 
                 AB009999_g_at 
                 NM_001263.2 
                 116 
                 840 
               
               
                 996 
                 AF008439_at 
                 NM_000617.1 
                 118 
                 841 
               
               
                 997 
                 AF037072_at 
                 NM_005181.2* 
                 121 
                 842 
               
               
                 998 
                 D64046_at 
                 NM_005027.1 
                 122 
                 843 
               
               
                 999 
                 AF077338_g_at 
                 NM_004997.1* 
                 124 
                 844 
               
               
                 1000 
                 D37920_at 
                 NM_003129.2 
                 128 
                 846 
               
               
                 1001 
                 M83298_g_at 
                 NM_002717.2 
                 132 
                 847 
               
               
                 1002 
                 M83676_at 
                 5410327 
                 133 
                 848 
               
               
                 1003 
                 rc_AA799571_at 
                 13491977 
                 137 
                 849 
               
               
                 1004 
                 M57263_at 
                 NM_000359.1 
                 140 
                 850 
               
               
                 1005 
                 rc_AA817975_at 
                 NM_005662.3 
                 145 
                 851 
               
               
                 1006 
                 rc_AA818745_at 
                 29488 
                 146 
                 852 
               
               
                 1007 
                 L27124_s_at 
                 NM_002525.1 
                 150 
                 853 
               
               
                 1008 
                 M18330_at 
                 NM_006254.2 
                 156 
                 854 
               
               
                 1009 
                 M32397_at 
                 NM_001099.2 
                 160 
                 855 
               
               
                 1010 
                 rc_AI227677_at 
                 D42055.1 
                 169 
                 856 
               
               
                 1011 
                 rc_AI230247_s_at 
                 NM_005410.1 
                 170 
                 857 
               
               
                 1012 
                 rc_AI171376_at 
                 NM_014332.1* 
                 181 
                 860 
               
               
                 1013 
                 rc_AI178921_s_at 
                 NM_004969.1 
                 192 
                 862 
               
               
                 1014 
                 rc_AI175935_at 
                 NM_004998.1* 
                 196 
                 863 
               
               
                 1015 
                 rc_AI176584_at 
                 NM_000599.1 
                 197 
                 864 
               
               
                 1016 
                 X52311_at 
                 NM_002524.2 
                 202 
                 865 
               
               
                 1017 
                 X64401cds_s_at 
                 BC003642 
                 207 
                 867 
               
               
                 1018 
                 X76489cds_g_at 
                 NM_001769.2 
                 212 
                 868 
               
               
                 1019 
                 Z78279_g_at 
                 BC036531 
                 215 
                 869 
               
               
                 1020 
                 Z83869cds_at 
                 NM_004954.2 
                 216 
                 870 
               
               
                 1021 
                 X64827cds_s_at 
                 J04823* 
                 217 
                 871 
               
               
                 1022 
                 rc_AI639324_at 
                 NM_030793 
                 219 
                 872 
               
               
                 1023 
                 rc_AI639465_f_at 
                 NM_032588.2* 
                 222 
                 874 
               
               
                 1024 
                 rc_H33725_at 
                 NM_006463.2 
                 224 
                 875 
               
               
                 1025 
                 X12554cds_s_at 
                 NM_005205.2 
                 227 
                 876 
               
               
                 1026 
                 U30938_at 
                 NM_002374.2 
                 229 
                 877 
               
               
                 1027 
                 U40836mRNA_s_at 
                 1311703 
                 230 
                 878 
               
               
                 1028 
                 S49760_at 
                 BC043292 
                 235 
                 879 
               
               
                 1029 
                 rc_AI011709_at 
                 35526 
                 241 
                 880 
               
               
                 1030 
                 rc_AA925122_at 
                 NM_000363 
                 255 
                 883 
               
               
                 1031 
                 rc_AA925664_at 
                 NM_001664 
                 257 
                 884 
               
               
                 1032 
                 rc_AA946108_at 
                 NM_173306 
                 270 
                 885 
               
               
                 1033 
                 rc_AI168935_at 
                 NM_018286 
                 271 
                 886 
               
               
                 1034 
                 rc_AI170894_at 
                 NM_001122 
                 285 
                 888 
               
               
                 1035 
                 rc_AI103376_at 
                 NM_018112 
                 289 
                 889 
               
               
                 1036 
                 rc_AI071299_at 
                 NM_005655.1 
                 290 
                 890 
               
               
                 1037 
                 rc_AI111401_s_at 
                 NM_004897.2 
                 295 
                 892 
               
               
                 1038 
                 rc_AI104354_at 
                 NM_016599 
                 303 
                 895 
               
               
                   
               
               
                   *Muscle-specific    
               
             
          
         
       
     
         [0107]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 9 
               
             
             
               
                   
               
               
                   
               
               
                 Human Protein SMNs 
               
             
          
           
               
                   
                   
                   
                 Table 8 
                   
               
               
                 SEQ ID 
                   
                 Accession 
                 SEQ ID 
                 Table 5 
               
               
                 NO: 
                 AffyID ™ 
                 Number 
                 NO: 
                 SEQ ID NO: 
               
               
                   
               
             
          
           
               
                 1039 
                 rc_AA946094_at 
                 P02144 
                 2 
                 963 
               
               
                 1040 
                 rc_AA891522_f_at 
                 P12883* 
                 3 
                 964 
               
               
                 1041 
                 rc_AA799471_at 
                 O15273 
                 4 
                 965 
               
               
                 1042 
                 M24393_at 
                 P15173* 
                 7 
                 966 
               
               
                 1043 
                 rc_AI012182_s_at 
                 P02023 
                 15 
                 967 
               
               
                 1044 
                 rc_AA818804_at 
                 Q9NWB1 
                 18 
                 968 
               
               
                 1045 
                 M12098_s_at 
                 P11055* 
                 20 
                 969 
               
               
                 1046 
                 M27151_at 
                 AAH17834* 
                 22 
                 970 
               
               
                 1047 
                 AF077338_at 
                 AAH44226* 
                 25 
                 971 
               
               
                 1048 
                 X74832cds_at 
                 P02708* 
                 26 
                 972 
               
               
                 1049 
                 AA108284_at 
                 P07451* 
                 29 
                 973 
               
               
                 1050 
                 rc_AI104913_at 
                 P28289* 
                 30 
                 974 
               
               
                 1051 
                 rc_AA818120_at 
                 O00631 
                 31 
                 975 
               
               
                 1052 
                 AF039832_g_at 
                 Q99697 
                 33 
                 976 
               
               
                 1053 
                 X15939_i_at 
                 P12883* 
                 34 
                 977 
               
               
                 1054 
                 X14812_at 
                 AAH09790* 
                 37 
                 978 
               
               
                 1055 
                 X15939_r_at 
                 P12883* 
                 39 
                 979 
               
               
                 1056 
                 rc_AI170696_at 
                 CAD62321 
                 51 
                 980 
               
               
                 1057 
                 rc_AA892801_at 
                 P13639 
                 61 
                 981 
               
               
                 1058 
                 rc_AA892287_at 
                 NP_061123.2 
                 66 
                 982 
               
               
                 1059 
                 rc_AA892313_at 
                 NP_003184.1 
                 67 
                 983 
               
               
                 1060 
                 rc_AA892468_g_at 
                 Q16651 
                 69 
                 984 
               
               
                 1061 
                 rc_AA859829_g_at 
                 NP_005873.1 
                 70 
                 985 
               
               
                 1062 
                 Z78279_at 
                 P02452 
                 81 
                 986 
               
               
                 1063 
                 rc_AA875206_at 
                 NP_038466.2 
                 85 
                 987 
               
               
                 1064 
                 rc_AA859931_g_at 
                 NP_076974.1 
                 87 
                 988 
               
               
                 1065 
                 rc_AA859335_at 
                 P23528* 
                 93 
                 989 
               
               
                 1066 
                 H32169_at 
                 NP_068733.1 
                 97 
                 990 
               
               
                 1067 
                 J04993_at 
                 AAH12600* 
                 102 
                 991 
               
               
                 1068 
                 L11694_at 
                 AAH19920 
                 103 
                 992 
               
               
                 1069 
                 D38056_at 
                 P20827 
                 105 
                 993 
               
               
                 1070 
                 L01702_at 
                 AAH27308 
                 108 
                 994 
               
               
                 1071 
                 AB009999_g_at 
                 Q92903 
                 116 
                 995 
               
               
                 1072 
                 AF008439_at 
                 BAB93467 
                 118 
                 996 
               
               
                 1073 
                 AF037072_at 
                 P07451* 
                 121 
                 997 
               
               
                 1074 
                 D64046_at 
                 O00459 
                 122 
                 998 
               
               
                 1075 
                 AF077338_g_at 
                 AAH44226* 
                 124 
                 999 
               
               
                 1076 
                 D37920_at 
                 Q14534 
                 128 
                 1000 
               
               
                 1077 
                 M83298_g_at 
                 AAH41071 
                 132 
                 1001 
               
               
                 1078 
                 M83676_at 
                 O88386 
                 133 
                 1002 
               
               
                 1079 
                 rc_AA799571_at 
                 Q9BXS4 
                 137 
                 1003 
               
               
                 1080 
                 M57263_at 
                 AAH34699 
                 140 
                 1004 
               
               
                 1081 
                 rc_AA817975_at 
                 Q9Y277 
                 145 
                 1005 
               
               
                 1082 
                 rc_AA818745_at 
                 Q01484 
                 146 
                 1006 
               
               
                 1083 
                 L27124_s_at 
                 O43847 
                 150 
                 1007 
               
               
                 1084 
                 M18330_at 
                 AAH43350 
                 156 
                 1008 
               
               
                 1085 
                 M32397_at 
                 P15309 
                 160 
                 1009 
               
               
                 1086 
                 rc_AI227677_at 
                 P46934 
                 169 
                 1010 
               
               
                 1087 
                 rc_AI230247_s_at 
                 P49908 
                 170 
                 1011 
               
               
                 1088 
                 rc_AI171376_at 
                 Q9UHP9* 
                 181 
                 1012 
               
               
                 1089 
                 rc_AI178921_s_at 
                 P14735 
                 192 
                 1013 
               
               
                 1090 
                 rc_AI175935_at 
                 Q12965* 
                 196 
                 1014 
               
               
                 1091 
                 rc_AI176584_at 
                 P24593 
                 197 
                 1015 
               
               
                 1092 
                 X52311_at 
                 AAH32446 
                 202 
                 1016 
               
               
                 1093 
                 X64401cds_s_at 
                 AAH03642 
                 207 
                 1017 
               
               
                 1094 
                 X76489cds_g_at 
                 P21926 
                 212 
                 1018 
               
               
                 1095 
                 Z78279_g_at 
                 P02452 
                 215 
                 1019 
               
               
                 1096 
                 Z83869cds_at 
                 Q15449 
                 216 
                 1020 
               
               
                 1097 
                 X64827cds_s_at 
                 P10176* 
                 217 
                 1021 
               
               
                 1098 
                 rc_AI639324_at 
                 NP_110420.1 
                 219 
                 1022 
               
               
                 1099 
                 rc_AI639465_f_at 
                 Q969Q1* 
                 222 
                 1023 
               
               
                 1100 
                 rc_H33725_at 
                 O95630 
                 224 
                 1024 
               
               
                 1101 
                 X12554cds_s_at 
                 AAH29818 
                 227 
                 1025 
               
               
                 1102 
                 U30938_at 
                 P11137 
                 229 
                 1026 
               
               
                 1103 
                 U40836mRNA_s_at 
                 P10176 
                 230 
                 1027 
               
               
                 1104 
                 S49760_at 
                 S12969 
                 235 
                 1028 
               
               
                 1105 
                 rc_AI011709_at 
                 Q15155 
                 241 
                 1029 
               
               
                 1106 
                 rc_AA925122_at 
                 TPHUCC 
                 255 
                 1030 
               
               
                 1107 
                 rc_AA925664_at 
                 A32342 
                 257 
                 1031 
               
               
                 1108 
                 rc_AA946108_at 
                 A55347 
                 270 
                 1032 
               
               
                 1109 
                 rc_AI168935_at 
                 NP_060756.1 
                 271 
                 1033 
               
               
                 1110 
                 rc_AI170894_at 
                 NP_001113.1 
                 285 
                 1034 
               
               
                 1111 
                 rc_AI103376_at 
                 NP_060582.1 
                 289 
                 1035 
               
               
                 1112 
                 rc_AI071299_at 
                 O75411 
                 290 
                 1036 
               
               
                 1113 
                 rc_AI111401_s_at 
                 O95172 
                 295 
                 1037 
               
               
                 1114 
                 rc_AI104354_at 
                 NP_057683.1 
                 303 
                 1038 
               
               
                   
               
               
                   *Muscle-specific    
               
             
          
         
       
     
         [0108]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 10 
               
             
             
               
                   
               
               
                   
               
               
                 Rat DNA BMNs 
               
             
          
           
               
                 SEQ 
                   
                   
                 Table 2 
               
               
                 ID 
                   
                 Accession 
                 SEQ 
               
               
                 NO: 
                 AffyID ™ 
                 Number 
                 ID NO: 
               
               
                   
               
               
                 1115 
                 rc_AI233261_i_at 
                 NM_017305 
                 N/A 
               
               
                 1116 
                 rc_AI012354_at 
                 NM_022647 
                 N/A 
               
               
                 1117 
                 rc_AA955974_at 
                 AA955974 
                 N/A 
               
               
                 1118 
                 rc_AI072712_at 
                 AI072712 
                 N/A 
               
               
                 1119 
                 rc_AI029088_at 
                 AI029088 
                 N/A 
               
               
                 1120 
                 X15939_i_at 
                 NM_017240* 
                 34 
               
               
                 1121 
                 rc_AA850730_at 
                 AA850730 
                 N/A 
               
               
                 1122 
                 rc_AA998245_at 
                 AA998245 
                 N/A 
               
               
                 1123 
                 rc_AI233173_at 
                 NM_138548 
                 N/A 
               
               
                 1124 
                 rc_AI232350_f_at 
                 AI232350 
                 N/A 
               
               
                 1125 
                 rc_AA998683_at 
                 NM_031970 
                 N/A 
               
               
                 1126 
                 rc_AA858921_at 
                 AA858921 
                 92 
               
               
                 1127 
                 rc_AA850705_at 
                 NM_153309 
                 N/A 
               
               
                 1128 
                 rc_AA998097_at 
                 AA998097 
                 N/A 
               
               
                 1129 
                 rc_AA997841_at 
                 NM_133298 
                 N/A 
               
               
                 1130 
                 rc_AA848449_at 
                 AA848449 
                 N/A 
               
               
                 1131 
                 rc_AA819268_at 
                 AA819268 
                 N/A 
               
               
                 1132 
                 rc_AA800268_at 
                 AA800268 
                 N/A 
               
               
                 1133 
                 M14050_s_at 
                 NM_013083 
                 N/A 
               
               
                 1134 
                 L06804_at 
                 L06804 
                 N/A 
               
               
                 1135 
                 D12769_at 
                 NM_057211 
                 N/A 
               
               
                 1136 
                 AF036335_g_at 
                 AF036335 
                 N/A 
               
               
                 1137 
                 AA801076_at 
                 AA801076 
                 N/A 
               
               
                 1138 
                 rc_AA848829_at 
                 AA848829 
                 N/A 
               
               
                 1139 
                 rc_AI030259_at 
                 AI030259 
                 N/A 
               
               
                 1140 
                 S69316_s_at 
                 S69316 
                 N/A 
               
               
                 1141 
                 rc_AI639155_at 
                 AI639155 
                 N/A 
               
               
                 1142 
                 rc_AI639012_at 
                 AI639012 
                 N/A 
               
               
                 1143 
                 rc_AI237654_at 
                 AI237654 
                 N/A 
               
               
                 1144 
                 rc_AI228696_at 
                 AI228696 
                 N/A 
               
               
                 1145 
                 rc_AI177055_at 
                 AI177055 
                 N/A 
               
               
                 1146 
                 rc_AI176969_at 
                 AI176969 
                 N/A 
               
               
                 1147 
                 rc_AI102438_at 
                 AI102438 
                 N/A 
               
               
                 1148 
                 rc_AI072603_at 
                 AI072603 
                 N/A 
               
               
                 1149 
                 rc_AI059519_at 
                 AI059519 
                 N/A 
               
               
                 1150 
                 rc_AA899491_at 
                 AA899491 
                 N/A 
               
               
                 1151 
                 rc_AI044635_at 
                 AI044635 
                 N/A 
               
               
                 1152 
                 rc_AA874873_g_at 
                 AA874873 
                 N/A 
               
               
                 1153 
                 rc_AI014091_at 
                 NM_053698 
                 N/A 
               
               
                 1154 
                 rc_AI013854_at 
                 AI013854 
                 N/A 
               
               
                 1155 
                 rc_AI012937_at 
                 AI012937 
                 N/A 
               
               
                 1156 
                 rc_AI008911_at 
                 AI008911 
                 N/A 
               
               
                 1157 
                 rc_AI007875_at 
                 NM_053435 
                 N/A 
               
               
                 1158 
                 rc_AI007672_at 
                 AI007672 
                 N/A 
               
               
                 1159 
                 rc_AA997726_at 
                 AA997726 
                 N/A 
               
               
                 1160 
                 rc_AA963457_at 
                 AA963457 
                 N/A 
               
               
                 1161 
                 rc_AA963171_at 
                 AA963171 
                 N/A 
               
               
                 1162 
                 rc_AA924573_s_at 
                 AA924573 
                 N/A 
               
               
                 1163 
                 rc_AI058912_at 
                 AI058912 
                 N/A 
               
               
                   
               
             
          
         
       
     
         [0109]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 11 
               
             
             
               
                   
               
               
                   
               
               
                 Rat Protein BMNs 
               
             
          
           
               
                 SEQ ID 
                   
                 Accession 
                 Table 10 
                 Table 2 
               
               
                 NO: 
                 AffyID ™ 
                 Number 
                 SEQ ID NO: 
                 SEQ ID NO: 
               
               
                   
               
               
                 1164 
                 rc_AI233261_i_at 
                 P48508 
                 1115 
                 N/A 
               
               
                 1165 
                 rc_AI012354_at 
                 64647 
                 1116 
                 N/A 
               
               
                 1166 
                 X15939_i_at 
                 P02564* 
                 1120 
                 34 
               
               
                 1167 
                 rc_AI233173_at 
                 Q05982 
                 1123 
                 N/A 
               
               
                 1168 
                 rc_AA998683_at 
                 P42930 
                 1125 
                 N/A 
               
               
                 1169 
                 rc_AA850705_at 
                 Q8CFC1 
                 1127 
                 N/A 
               
               
                 1170 
                 rc_AA997841_at 
                 Q9QZF6 
                 1129 
                 N/A 
               
               
                 1171 
                 M14050_s_at 
                 P06761 
                 1133 
                 N/A 
               
               
                 1172 
                 L06804_at 
                 P36198 
                 1134 
                 N/A 
               
               
                 1173 
                 D12769_at 
                 Q01713 
                 1135 
                 N/A 
               
               
                 1174 
                 AF036335_g_at 
                 O54725 
                 1136 
                 N/A 
               
               
                 1175 
                 S69316_s_at 
                 S69316 
                 1140 
                 N/A 
               
               
                 1176 
                 rc_AI237654_at 
                 117514 
                 1143 
                 N/A 
               
               
                 1177 
                 rc_AI014091_at 
                 Q99MA1 
                 1153 
                 N/A 
               
               
                 1178 
                 rc_AI007875_at 
                 Q9ESZ0 
                 1157 
                 N/A 
               
               
                   
               
               
                   *Muscle-specific    
               
             
          
         
       
     
         [0110]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 12 
               
             
             
               
                   
               
               
                   
               
               
                 Human DNA BMNs 
               
             
          
           
               
                   
                   
                   
                   
                 Table 4 
               
               
                 SEQ ID 
                   
                 Accession 
                 Table 10 
                 SEQ ID 
               
               
                 NO: 
                 AffyID ™ 
                 Number 
                 SEQ ID NO: 
                 NO: 
               
               
                   
               
               
                 1179 
                 rc_AI233261_i_at 
                 NM_002061.1 
                 1115 
                 N/A 
               
               
                 1180 
                 rc_AI012354_at 
                 NM_022647 
                 1116 
                 N/A 
               
               
                 1181 
                 rc_AA955974_at 
                 NM_001851 
                 1117 
                 N/A 
               
               
                 1182 
                 X15939_i_at 
                 NM_000257.1* 
                 1120 
                 490 
               
               
                 1183 
                 rc_AA850730_at 
                 505095 
                 1121 
                 N/A 
               
               
                 1184 
                 rc_AI233173_at 
                 NM_000269.1 
                 1123 
                 N/A 
               
               
                 1185 
                 rc_AA998683_at 
                 NM_031970 
                 1125 
                 N/A 
               
               
                 1186 
                 rc_AA850705_at 
                 213189_at 
                 1127 
                 N/A 
               
               
                 1187 
                 rc_AA998097_at 
                 1000283 
                 1128 
                 N/A 
               
               
                 1188 
                 rc_AA997841_at 
                 NM_002510.1 
                 1129 
                 N/A 
               
               
                 1189 
                 rc_AA800268_at 
                 NM_014182 
                 1132 
                 N/A 
               
               
                 1190 
                 M14050_s_at 
                 NM_005347.2 
                 1133 
                 N/A 
               
               
                 1191 
                 L06804_at 
                 600494 
                 1134 
                 N/A 
               
               
                 1192 
                 D12769_at 
                 NM_001206.1 
                 1135 
                 N/A 
               
               
                 1193 
                 AF036335_g_at 
                 NM_005066.1 
                 1136 
                 N/A 
               
               
                 1194 
                 rc_AI030259_at 
                 NM_031219 
                 1139 
                 N/A 
               
               
                 1195 
                 rc_AI639012_at 
                 NM_024042 
                 1142 
                 N/A 
               
               
                 1196 
                 rc_AI237654_at 
                 NM_006472.1 
                 1143 
                 N/A 
               
               
                 1197 
                 rc_AI228696_at 
                 NM_012106 
                 1144 
                 N/A 
               
               
                 1198 
                 rc_AI177055_at 
                 NM_053050 
                 1145 
                 N/A 
               
               
                 1199 
                 rc_AI059519_at 
                 NM_024324 
                 1149 
                 N/A 
               
               
                 1200 
                 rc_AA899491_at 
                 XM_291885 
                 1150 
                 N/A 
               
               
                 1201 
                 rc_AI044635_at 
                 NM_014934 
                 1151 
                 N/A 
               
               
                 1202 
                 rc_AI014091_at 
                 NM_006079.2 
                 1153 
                 N/A 
               
               
                 1203 
                 rc_AI012937_at 
                 NM_013442 
                 1155 
                 N/A 
               
               
                 1204 
                 rc_AI008911_at 
                 NM_012470 
                 1156 
                 N/A 
               
               
                 1205 
                 rc_AI007875_at 
                 203655_at 
                 1157 
                 N/A 
               
               
                 1206 
                 rc_AA997726_at 
                 1136429 
                 1159 
                 N/A 
               
               
                 1207 
                 rc_AA963171_at 
                 NM_031210 
                 1161 
                 N/A 
               
               
                   
               
               
                   *Muscle-specific    
               
             
          
         
       
     
         [0111]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 13 
               
             
             
               
                   
               
               
                   
               
               
                 Human Protein BMNs 
               
             
          
           
               
                 SEQ 
                   
                   
                 Table 12 
                   
               
               
                 ID 
                   
                 Accession 
                 SEQ ID 
                 Table 5 
               
               
                 NO: 
                 AffyID ™ 
                 Number 
                 NO: 
                 sSEQ ID NO: 
               
               
                   
               
               
                 1208 
                 rc_AI233261_i_at 
                 AAH41809 
                 1115 
                 1179 
               
               
                 1209 
                 rc_AI012354_at 
                 E40335 
                 1116 
                 1180 
               
               
                 1210 
                 rc_AA955974_at 
                 NP_001842.2 
                 1117 
                 1181 
               
               
                 1211 
                 X15939_i_at 
                 P12883* 
                 1120 
                 1182 
               
               
                 1212 
                 rc_AA850730_at 
                 Q15040 
                 1121 
                 1183 
               
               
                 1213 
                 rc_AI233173_at 
                 P15531 
                 1123 
                 1184 
               
               
                 1214 
                 rc_AA998683_at 
                 HHHU27 
                 1125 
                 1185 
               
               
                 1215 
                 rc_AA850705_at 
                 NP_116167.1 
                 1127 
                 1186 
               
               
                 1216 
                 rc_AA998097_at 
                 P49903 
                 1128 
                 1187 
               
               
                 1217 
                 rc_AA997841_at 
                 Q14956 
                 1129 
                 1188 
               
               
                 1218 
                 rc_AA800268_at 
                 NP_054901.1 
                 1132 
                 1189 
               
               
                 1219 
                 M14050_s_at 
                 AAH20235 
                 1133 
                 1190 
               
               
                 1220 
                 L06804_at 
                 P50458 
                 1134 
                 1191 
               
               
                 1221 
                 D12769_at 
                 Q13886 
                 1135 
                 1192 
               
               
                 1222 
                 AF036335_g_at 
                 P23246 
                 1136 
                 1193 
               
               
                 1223 
                 rc_AI030259_at 
                 NP_112496.1 
                 1139 
                 1194 
               
               
                 1224 
                 rc_AI639012_at 
                 NP_076947.1 
                 1142 
                 1195 
               
               
                 1225 
                 rc_AI237654_at 
                 Q16226 
                 1143 
                 1196 
               
               
                 1226 
                 rc_AI228696_at 
                 NP_036238.1 
                 1144 
                 1197 
               
               
                 1227 
                 rc_AI177055_at 
                 NP_444278.1 
                 1145 
                 1198 
               
               
                 1228 
                 rc_AI059519_at 
                 NP_077300.1 
                 1149 
                 1199 
               
               
                 1229 
                 rc_AA899491_at 
                 A41706 
                 1150 
                 1200 
               
               
                 1230 
                 rc_AI044635_at 
                 NP_055749.1 
                 1151 
                 1201 
               
               
                 1231 
                 rc_AI014091_at 
                 Q99967 
                 1153 
                 1202 
               
               
                 1232 
                 rc_AI012937_at 
                 NP_038470.1 
                 1155 
                 1203 
               
               
                 1233 
                 rc_AI008911_at 
                 NP_036602.1 
                 1156 
                 1204 
               
               
                 1234 
                 rc_AI007875_at 
                 A36353 
                 1157 
                 1205 
               
               
                 1235 
                 rc_AA997726_at 
                 Q14690 
                 1159 
                 1206 
               
               
                 1236 
                 rc_AA963171_at 
                 NP_112487.1 
                 1161 
                 1207 
               
               
                   
               
               
                   *Muscle-specific    
               
             
          
         
       
     
       EXAMPLES  
       [0000]     Spinal Nerve Ligation and Artemin Treatment  
         [0112]     Male Srague-Dawley rats were subjected to unilateral spinal nerve ligation (SNL) performed according to the procedure of Kim and Chung (1992) Pain, 50:355-365. Rats with motor deficiency were excluded. The L 5  and L 6  spinal nerves of anesthetized rats were exposed and tightly ligated with 4-0 silk sutures. Sham surgery was identical but without actual ligation.  
         [0113]     Rat artemin (113 amino acids; SEQ ID NO:1237) was isolated and refolded from  E. coli  inclusion bodies and purified to &gt;98% homogeneity (Gardell et al. (2003) Nature Med., 9(11):1383-1389). (The amino acid sequence of human artemin is set out in SEQ ID NO:1238). The purified artemin migrated as a reducible dimer by SDS-PAGE and eluted as a single peak (24 kDa) by size exclusion chromatography and by reverse phase HPLC. The purified product was confirmed to contain the characteristic cysteine knot disulfide pattern seen in GDNF, and to be fully active in vitro by assaying receptor binding, cell-based c-RET kinase activation (Sanicola et al. (1997) Proc. Natl. Acad. Sci. USA, 94:6238-6243) and sensory neuronal survival. Artemin (1 mg/kg) was injected subcutaneously on days 3, 5, 7, 10, 12 and 14 following spinal nerve ligation surgery.  
         [0000]     Behavioral Assays  
         [0114]     Hyperalgesia to thermal stimulation was assessed as described by Hargreaves et al. (1988) Pain, 32:77-88. Latency to withdrawal of a hindpaw in response to noxious radiant heat was determined. A maximal cut-off of 40 sec prevented tissue damage.  
         [0115]     Tactile withdrawal thresholds were measured by probing the hindpaw with 8 calibrated von Frey filaments (Stoelting, Wood Dale, Ill.) (0.41 g to 15 g). Each filament was applied to the plantar surface of the hindpaw using the up-down method as described by Chaplan et al. (1994) J. Neurosci. Methods, 53, 55-63. Withdrawal threshold was determined by sequentially increasing and decreasing the stimulus strength and calculated with a Dixon non-parametric test (Dixon (1980) Ann. Rev. Pharmacol. Toxicol., 20:441-462).  
         [0116]     Following behavioral confirmation of nerve ligation-induced tactile and thermal hyperalgesia, and efficacy of artemin on neuropathic pain behavior, skin samples were collected on day 14 post-spinal nerve ligation (following artemin injection and behavioral testing) from L4 dermatomes for subsequent gene expression profiling. The skin was shaved to remove as much hair as possible, and 12 skin samples in total were collected and snap-frozen, comprising triplicates from each of 4 groups of rats: (1) vehicle treated+SNL injury (ipsilateral to injury), (2) vehicle treated+SNL injury (contralateral to injury), (3) artemin treated+SNL injury (ipsilateral to injury), and (4) artemin treated+SNL injury (contralateral to injury).  
         [0000]     Total RNA Purification  
         [0117]     Snap frozen skin samples were homogenized using an Ultra-Turrax T8 (IKA-Werke, Staufen, Germany) in TRIzol™ reagent (Invitrogen Life Technologies, Carlsbad, Calif.) according to manufacturer&#39;s protocol. 100 μg of total RNA was further purified using an RNeasy™ Mini column (Qiagen, Valencia, Calif.) according to manufacturer&#39;s protocol.  
         [0000]     Probe Labeling Hybridization and Scanning  
         [0118]     The mRNA from skin biopsies samples was profiled on Affymetrix Rat Genome U34A, U34B, and U34C GeneChips™ probe arrays. These arrays contain more than 24,000 mRNA transcripts from gene and EST sequences found in Build 34 of the UniGene™ Database with additional full-length sequences from GenBank™ 110. GeneChip™ probe arrays are made by synthesizing oligonucleotide probes directly onto a glass surface. Each 25mer oligonucleotide probe is uniquely complementary to a gene, with approximately 16 pairs of oligonucleotide probes used to measure the transcript level of each of the genes represented in the array.  
         [0119]     Sample labeling, hybridization, and staining were carried out according to the Eukaryotic Target Preparation protocol in the Affymetrix™ Technical Manual (701021 rev 1) for GeneChip™ Expression Analysis (Affymetrix, Santa Clara, Calif.). In summary, 5 μg of purified total RNA was used in a 20 μL first strand reaction with 200 U SuperScript™ 11 (Invitrogen Life Technologies, Carlsbad, Calif.) and 0.5 μg (dT)-T7 primer (SEQ ID NO:1239) in 1× first strand buffer (Invitrogen, Carlsbad, Calif.) with a 42° C. incubation for 1 hour. Second strand synthesis was carried out by the addition of 40 U of  E. coli  DNA Polymerase, 2 U of  E. coli  RNase H, 10 U of  E. coli  DNA ligase in 1× second strand buffer (Invitrogen) followed by incubation at 16° C. for 2 hrs. The second strand synthesis reaction was purified using the GeneChip™ Sample Cleanup Module according to the manufacturer&#39;s protocol (Affymetrix). The purified cDNA was amplified using BioArray™ high yield RNA transcription labeling kit (Enzo Life Sciences, Parmingdale, N.Y.) according to manufacturer&#39;s protocol to produce 70-120 μg of biotin labeled cRNA (compliment RNA). Rat Genome U34 A, B, and C GeneChip™ probe arrays were pre-hybridized in a GeneChip™ Hybridization Oven 640 (Affymetrix) according to the manufacturer&#39;s protocol. Fifteen μg of labeled cRNA was fragmented in 30 μL 1× fragmentation buffer 100 mM KOAc, 30 mM MgOAc at 95° C. for 35 minutes. The fragmented labeled cRNA was resuspended in 300 μL 1× hybridization buffer containing 100 mM MES, 1 M Na + , 20 mM EDTA, 0.01% Tween™ 20, 0.5 mg/mL acetylated BSA, 0.1 mg/mL herring sperm DNA, control oligo B2, and control transcripts bioB 1.5 pM, bioC 5 pM, bioD 25 pM, and cre 100 pM, and hybridized to GeneChip™ probe arrays according to manufacturer&#39;s protocol (Affymetrix, Santa Clara, Calif.). The hybridized GeneChip® probe arrays were washed and stained using streptavidin-phycoerythrinin (Molecular Probes, Eugene, Oreg.) and amplified with biotinylated anti-streptavidin (Vector Laboratories, Burlingame, Calif.) (Sigma, Saint Louis, Mo.) GeneChip™ Fluidics Station 400 (Affymetrix) using an antibody amplification protocol. The GeneChip™ probe arrays were scanned using GeneArray™ scanner (Hewlett Packard, Corvallis, Oreg.).  
         [0000]     Data Analysis  
         [0120]     Two independent analysis approaches (Rosetta Resolver™ and a proprietary permutation-based Bayesian statistical model) were used to identify bio- and surrogate markers.  
         [0121]     The following analysis techniques were performed using Rosetta Resolver™ software (Rosetta Biosoftware, Kirkland, Wash.).  
         [0122]     The triplicate samples were considered a single group for ANOVA analyses. The comparisons of interest include the following: 
        1) Vehicle-treated vs. artemin-treated contralateral dermatomes;     2) Vehicle-treated vs. artemin-treated ipsilateral dermatomes;     3) Contralateral vs. ipsilateral vehicle-treated dermatomes;     4) Contralateral vs. ipsilateral artemin-treated dermatomes.        
 
         [0127]     A gene list was generated based on those genes whose expression level was found to be significantly different between groups (p≦0.01). These genes Were subsequently tested for significance (p≦0.01) in fold-change values. The final gene list for each of the 4 comparisons included those genes that passed both criteria. Agglomerative hierarchical clustering techniques (heuristic criteria=average link, similarity measure=Euclidean distance, intensity/Z-score used for clustering) ensured that these final gene lists differentiated well the two populations in each comparison from each other.  
         [0128]     Permutation-based Bayesian Analysis was performed as follows. For all genes, a permutation based approach was used to generate distributions of log ratios of the expression intensity values for all possible pairwise within group (between replicates) and between group comparisons of the samples.  
         [0129]     For example, the 3 replicate rats generated 3 within-group pairwise comparisons for each of the 4 treatment scenarios outlined above. In this way, a total of 12 within-group log ratios and 9 between-group log ratios for the 6 possible between-group comparisons were generated (Table 14). This was done for the A, B, and C chips.  
                           TABLE 14                       Comparison           No. of pairwise       type   Group 1   Group 2   comparisons                   Between   Vehicle-treated,   Vehicle-treated,   9       group   ipsilateral   contralateral           (3 replicate rats)   (3 replicate rats)       Between   artemin-treated,   artemin-treated,   9       group   ipsilateral   contralateral           (3 replicate rats)   (3 replicate rats)       Between   artemin-treated,   Vehicle-treated,   9       group   ipsilateral   ipsilateral           (3 replicate rats)   (3 replicate rats)       Between   artemin-treated,   Vehicle-treated,   9       group   ipsilateral   contralateral           (3 replicate rats)   (3 replicate rats)       Between   Vehicle-treated,   artemin-treated,   9       group   ipsilateral   contralateral           (3 replicate rats)   (3 replicate rats)       Between   artemin-treated,   Vehicle-treated,   9       group   contralateral   contralateral           (3 replicate rats)   (3 replicate rats)       Within group   Vehicle-treated,   Vehicle-treated,   3           ipsilateral   ipsilateral           (3 replicate rats)   (3 replicate rats)       Within group   Vehicle-treated,   Vehicle-treated,   3           contralateral   contralateral           (3 replicate rats)   (3 replicate rats)       Within group   artemin-treated,   artemin-treated,   3           ipsilateral   contralateral           (3 replicate rats)   (3 replicate rats)       Within group   artemin-treated,   artemin-treated,   3           contralateral   contralateral           (3 replicate rats)   (3 replicate rats)                  
 
         [0130]     All ratio calculations were performed using the Affymetrix™ MAS5 application that summarizes the ratios of background corrected intensities (perfect match minus the mismatch intensity values) using an Affymetrix™ proprietary error model described in Affymetrix Microarray Suite User&#39;s guide Version 5.0 (2001). Default parameters were used to quantify signal intensities (Alpha1=0.04; Alpha2=0.06; Tau=0.015; Noise (RawQ)=2.800; Scale Factor (SF)=1.000 Norm Factor (NF)=1.000; Gamma1L=0.0025; Gamma1H=0.0025; Gamma2L=0.003; Gamma2H=0.003; Perturbation=1.1). The summarized signal log ratios with their associated P values were exported for statistical analysis.  
         [0131]     The prior distribution of the log ratios were used to update the P values (posterior probability) of the between group comparison log ratios. Genes with between group log ratio distributions that significantly (p&lt;0.05) differed from the within group distribution of log ratios were selected as differentially expressed genes. The summary log ratio for any comparison was estimated as an error-weighted mean of all the permuted log ratios in that group.  
         [0132]     308 genes that are affected by spinal nerve ligation injury (vehicle-treated ipsilateral vs. contralateral dermatomes) and that therefore correlate with neuropathic pain behavior are listed in Table 2.  
         [0133]     To identify surrogate markers of artemin neurotrophic activity, genes with specific profiles of interest (e.g., genes that were up-regulated after injury and then down-regulated to normal levels with administration of artemin) were found by intersecting the lists of genes comparing contralateral vs. ipsilateral vehicle-treated dermatomes and vehicle-treated vs. artemin-treated ipsilateral dermatomes. 107 surrogate markers of artemin neurotrophic activity thus identified are listed in Table 6.  
         [0134]     To identify biomarkers of artemin&#39;s in vivo biological activity, genes in common on the lists comparing vehicle-treated vs. artemin-treated contralateral dermatomes and vehicle-treated vs. artemin-treated ipsilateral dermatomes were identified. Genes were then identified that are regulated in the same direction by artemin in the contralateral and ipsilateral dermatomes. 49 biomarkers of artemin biological activity were thus identified and are listed in Table 10.  FIG. 7  shows an example of a BMN that has not been confirmed by TaqMan™ analysis.  
         [0135]     To confirm the validity of surrogate markers and biomarkers, 25 preferred surrogate markers of neurotrophic activity and 5 preferred biomarkers were used for sequence analysis to validate the existence of transcripts. The sequence analysis included a BLAST™ search of the Affymetrix™ target sequence against the rat genomic sequence. The genomic locus was then examined for the existence of exons, ESTs, and predicted transcripts. The genes are prioritized based on transcript evidence and subjected to TaqMan™ validation as described below (see, also, Holland et al. (1991). Proc. Natl. Acad. Sci. USA, 88:7276-7280).  
         [0000]     TaqMan™ Analysis  
         [0136]     Trizol™ (Invitrogen) purified rat skin RNA was further re-purified using an RNeasy™ Mini kit (Qiagen) according to the manufacturer&#39;s protocol. The RNA was digested with Amplification Grade Deoxyribonuclease 1 (Invitrogen) to remove any contaminating DNA, and was subsequently used as a template for cDNA synthesis with a High-Capacity cDNA Archive Kit (Applied Biosystems). The resulting cDNA was used as the PCR template for TaqMan™ analysis.  
         [0137]     The “TaqMan MGB Probe and Primer Design” function of Primer Express 1.5 software (Applied Biosystems) was used to generate primer and probe sequences for Affymetrix target sequences (for example, see Table 15 for rc_AA818804_at RG-U34C, rc_aa818120_at RG-U34C, and X14812_at RG-U34A).  
                                   TABLE 15                                   Forward   Reverse               Marker   Amplicon   primer   primer   Probe           SEQ   SEQ   SEQ   SEQ   SEQ       AffyID ™   ID NO:   ID NO:   ID NO:   ID NO:   ID NO:                   rc_AA818120_at   31,808   1240   1241   1242   1243       RG-U34C       rc_AA818804_at   18,799   1244   1245   1246   1247       RG-U34C       X14812_at   13 813   1248   1249   1250   1251       RG-U34A                  
 
         [0138]     Oligomers spanning the PCR amplicon, plus an additional 10 bp on the 5′ and 3′ ends of each gene were also synthesized. Primers and 6FAM-labeled probes were synthesized by Applied Biosystems, and set up in reactions with the cDNA templates according to standard methods. Reactions were carried out in an ABI Prism™ 7700 Sequence Detector using the default conditions, and the data was analyzed using Sequence Detection Software v1.9.1 (Applied Biosystems). Simultaneous PCR reactions were carried out using a 10-fold dilutions series of the amplicon oligomers to generate a standard curve for each primer and probe set. Cycle Threshold (Ct) values for each experimental reaction were compared to the amplicon standard curve and relative quantities of message were determined. The cDNA samples were also analyzed with TaqMan™ Rodent GAPDH Control Reagents (Applied Biosystems) to determine the amount of GAPDH message in each sample. The samples were normalized by dividing the signal for each of the surrogate marker genes by the signal obtained with the GAPDH control. The results are shown in  FIGS. 1-6 .  
         [0139]     The expression patterns of the genes shown in  FIGS. 1-6  parallel the results of the Affymetrix analysis. All of these genes are expressed at a low level in the uninjured state (vehicle/contralateral and artemin/contralateral), are up-regulated in the injured state (vehicle/ipsilateral), and are at least partially normalized following artemin treatment (artemin/ipsilateral). The expression profiles are consistent with these genes acting as surrogate markers of artermin activity in the rat spinal nerve ligation model.  
         [0140]     All references to nucleotide sequences should be understood to encompasses their sequences complementary to a given sequence. All publications and patents and sequences cited in this disclosure by their accession numbers are incorporated by reference in their entirety. To the extent the material incorporated by reference contradicts or is inconsistent with the present specification, the specification will supercede any such material.  
         [0141]     The material submitted herewith on the CD-ROM entitled “Surrogate Markers of Neuropathic Pain,” containing file surrmarkers012504.5T25.txt, size on disk 4,515,840 bytes, created on Feb. 20, 2004, is hereby incorporated by reference.  
         [0142]     The specific embodiments described herein are offered by way of example only and are not meant to be limiting in any way. It is intended that the specification and examples be considered as illustrative only, with a true scope and spirit of the invention being indicated by the following claims.
The disclosure provides methods and compositions for the evaluation of neuropathic pain and neurotrophic or other activity of a drug or drug candidate. In the disclosed methods, expression of certain gene(s) in tissue extracts from skin biopsies serves as a proxy of a relevant endpoint.