DRG11-Responsive (DRAGON) Gene Family

Abstract

This invention features methods and compositions useful for treating and diagnosing diseases of the nervous system, retina, skin, muscle, joint, and cartilage using a Dragon family protein. Protein and nucleic acid sequences of human, murine, zebrafish, and C. elegans Dragon family members are also disclosed.

1 . A method for diagnosing a human patient as having, or having an increased risk of developing, a Dragon-related condition comprising taking a biological from the patient and determining if a nucleic acid sequence of SEQ ID NO: 31 contains a mutation relative to SEQ ID NO: 31, wherein SEQ ID NO: 31 encodes a protein having the amino acid sequence of SEQ ID NO: 9, which results in the encoded protein having an increase or decrease in the biological activity of said protein relative to the biological activity of the wild type protein encoded by the nucleic acid sequence SEQ ID NO: 31, wherein said biological activity is promotion of adhesion of cultured dorsal root ganglion (DRG) neurons, wherein if the human patient has the mutation, the human patient has or is at risk of having a Dragon-related condition. 
     
     
         2 . The method of  claim 1 , wherein assessing comprises the polymerase chain reaction. 
     
     
         3 . The method of  claim 1 , wherein assessing comprises restriction fragment length polymorphism (RFLP) analysis. 
     
     
         4 . The method of  claim 1 , wherein the dragon-related condition is a neurological disorder. 
     
     
         5 . The method of  claim 6 , wherein the neurological disorder is a neurodegenerative disease or disorder. 
     
     
         6 . The method of  claim 1 , wherein the mutation occurs in a region of the nucleic acid which encodes a conserved domain of the protein. 
     
     
         7 . The method of  claim 1 , wherein the mutation is in the coding region of the nucleic acid sequence of SEQ ID NO: 31, which leads to reduction of protein function. 
     
     
         8 . The method of  claim 1 , wherein the mutation which leads to impairment of gene expression is in an untranslated region of the nucleic acid sequence of SEQ ID NO: 31. 
     
     
         9 . The method of  claim 1 , wherein the mutation is in a promoter region which is operatively linked to the gene. 
     
     
         10 . The method of  claim 1 , wherein the mutation is detected by a mismatch detection assay. 
     
     
         11 . The method of  claim 1 , wherein the mutation is in the splice donor site of exon 1. 
     
     
         12 . The method of  claim 1 , wherein the mutation results in a truncated protein. 
     
     
         13 . The method of  claim 14 , wherein the truncated protein lacks the GPI anchor domain. 
     
     
         14 . A method for diagnosing a human patient as having or having an increased risk of developing a Dragon-related condition comprising taking a biological sample from the patient and determining the expression level of a nucleic acid and/or protein, wherein the nucleic acid sequence is SEQ ID NO: 31 and the protein is SEQ ID NO: 9, wherein if an increase or decrease in the expression level of the nucleic acid and/or the protein is detected relative to a control sample, the human patient has or is at risk of having, or having an increased risk of developing Dragon-related condition.