Human uridine diphosphate galactose-4-epimerase

Abstract

A human UDP galactose-4-epimerase polypeptide and DNA (RNA) encoding such polypeptide and a procedure for producing such polypeptide by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptide for the treatment of galactosemia. Also disclosed are diagnostic assays for the detection of mutations in the nucleic acid sequencing encoding human UDP galactose-4-epimerase protein and for detecting an altered level of human UDP galactose-4-epimerase protein in a sample derived from a host.

What is claimed is:  
     
         1 . An isolated polynucleotide comprising a member selected from the group consisting of: 
 (a) a polynucleotide encoding the polypeptide as set forth in SEQ ID NO:2;    (b) a polynucleotide capable of hybridizing to and which is at least 70% identical to the polynucleotide of (a); and    (c) a fragment of the polynucleotides of (a) or (b), said fragment being at least 50 base pairs in length.    
     
     
         2 . The polynucleotide of  claim 1  comprising nucleotide 1 to nucleotide 1249 as set forth in SEQ ID NO:1.  
     
     
         3 . The polynucleotide of  claim 1  comprising nucleotide 93 to nucleotide 1136 as set forth in SEQ ID NO:1.  
     
     
         4 . The polynucleotide of  claim 1  wherein the polynucleotide is DNA.  
     
     
         5 . An isolated polynucleotide comprising a member selected from the group consisting of: 
 (a) a polynucleotide encoding the mature polypeptide encoded by the DNA contained in ATCC Deposit No. 97112;    (b) a polynucleotide encoding the polypeptide expressed by the DNA contained in ATCC Deposit No. 97112;    (c) a polynucleotide capable of hybridizing to and which is at least 90% identical to the polynucleotide of (a) or (b); and    (d) a polynucleotide fragment of the polynucleotide of (a), (b) or (c), said polynucleotide fragment being at least 50 base pairs in length.    
     
     
         6 . The polynucleotide of  claim 5  wherein said polynucleotide encodes a mature polypeptide encoded by the DNA contained in ATCC Deposit No. 97112.  
     
     
         7 . The polynucleotide of  claim 5  wherein said polynucleotide encodes the polypeptide expressed by the DNA contained in ATCC Deposit No. 97112.  
     
     
         8 . A vector containing the polynucleotide of  claim 1 .  
     
     
         9 . A host cell transformed or transfected with the vector of  claim 8 .  
     
     
         10 . A process for producing a polypeptide comprising: expressing from the host cell of  claim 9  the polypeptide encoded by said DNA.  
     
     
         11 . A process for producing cells capable of expressing a human UDP galactose-4-epimerase polypeptide comprising culturing the recombinant host cell of  claim 9  under conditions promoting expression of said polypeptide and recovery thereof.  
     
     
         12 . A polypeptide comprising a member selected from the group consisting of: 
 (a) a polypeptide having the deduced amino acid sequence as set forth in SEQ ID NO:2 and fragments, analogs and derivatives thereof; and    (b) a polypeptide encoded by the cDNA of ATCC Deposit No. 97112 and fragments, analogs and derivatives of said polypeptide.    
     
     
         13 . The polypeptide of  claim 12  wherein the polypeptide comprises the deduced amino acid sequence as set forth in SEQ ID NO:2.  
     
     
         14 . An antibody against the polypeptide of  claim 12 .  
     
     
         15 . A compound which enhances interaction of the polypeptide of  claim 12  and a substrate.  
     
     
         16 . A method for the treatment of a patient having need of human UDP galactose-4-epimerase comprising: administering to the patient a therapeutically effective amount of the polypeptide of  claim 12 .  
     
     
         17 . The method of  claim 16  wherein said therapeutically effective amount of the polypeptide is administered by providing to the patient DNA encoding said polypeptide and expressing said polypeptide in vivo.  
     
     
         18 . A method for treating conditions which are related to insufficient human UDP galactose-4-epimerase activity comprising: 
 administering to a patient in need thereof a therapeutically effective amount of the polypeptide of  claim 12  to thereby alleviate said conditions.    
     
     
         19 . A method for diagnosing conditions associated with human UDP galactose-4-epimerase deficiency which comprises: 
 detecting mutations in the polynucleotide of  claim 1.