Polycystic xidney disease PKD2 gene and uses thereop

Abstract

The present invention provides a purified and isolated wild type PKD2 gene, as well as mutated forms of this gene. The present invention also provides one or more single-stranded nucleic acid probes which specifically hybridize to the wild type PKD2 gene or the mutated PKD2 gene, and mixtures thereof, which may be formulated in kits, and used in the diagnosis of ADPKD associated with the mutated PKD2 gene. The present invention also provides a method for diagnosing ADPKD caused by a mutated PKD2 gene, as well as a method for treating autosomal dominant polycystic kidney disease caused by a mutated PKD2 gene.

1 - 75 . (canceled)  
     
     
         76 . A method of diagnosing autosomal dominant kidney disease in a human comprising detecting the presence of a mutated polycystic kidney disease type 2 (PKD2) gene in a polynucleotide sample obtained from the human, wherein a mutated PKD2 gene results in the absence of expression of PKD2 protein, a reduction in the level of expression of PKD2 protein, or the expression of a non-functional PKD2 protein.  
     
     
         77 . A method for determining whether a human is at risk for development of autosomal dominant polycystic kidney disease, the method comprising: 
 a) assaying a polynucleotide sample containing a polycystic kidney disease type 2 (PKD2) gene from the human to determine the presence or absence of a mutated PKD2 gene comprising determining the nucleic acid sequence of all of, or a portion of, the PKD2 gene in the sample; and    b) comparing the nucleic acid sequence of the PKD2 gene, or portion thereof, in the sample to the nucleic acid sequence of a control PKD2 gene comprising SEQ ID NO: 6 and determining if there are any mutations in the human PKD2 gene that would result in the absence of, or reduction in the level of, expression of the encoded PKD2 protein, or in the expression of a non-functional PKD2 protein,    wherein the presence of a mutated PKD2 gene in the sample resulting in the absence of expression of PKD2 protein, a reduction in the level of expression of PKD2 protein, or the expression of a non-functional PKD2 protein, is indicative of the human being at risk for development of autosomal polycystic kidney disease.    
     
     
         78 . The method of  claim 77 , wherein the nucleic acid sequence of the PKD2 gene is determined by one or more techniques selected from the group consisting of: direct sequencing, single strand conformational analysis, restriction enzyme digestion analysis, nuclei acid probe hybridization and polymerase chain reaction.  
     
     
         79 . The method of  claim 77 , wherein the mutated PKD2 gene contains one or more deletion, insertion, point or rearrangement mutations, or a combination thereof, that render the gene product encoded or expressed by the mutated gene non-functional or non-existent.  
     
     
         80 . The method of  claim 78 , wherein the nucleic acid probe comprises 12 to 40 nucleotides in length of SEQ ID NO: 6.  
     
     
         81 . A method for determining whether a human has autosomal dominant polycystic kidney disease, the method comprising: 
 a) assaying a polynucleotide sample containing a polycystic kidney disease type 2 (PKD2) gene from the human to determine the presence or absence of a mutated PKD2 gene comprising determining the nucleic acid sequence of all of, or a portion of, the PKD2 gene in the sample; and    b) comparing the nucleic acid sequence of the PKD2 gene, or portion thereof, in the sample to the nucleic acid sequence of a control PKD2 gene comprising SEQ ID NO: 6 and determining if there are any mutations in the human PKD2 gene that would result in the absence of, or reduction in the level of, expression of the encoded PKD2 protein, or in the expression of a non-functional PKD2 protein,    wherein the presence of a mutated PKD2 gene in the sample resulting in the absence of the expression of PKD2 protein, a reduction in the level of expression of PKD2 protein, or the expression of a non-functional PKD2 protein, is indicative of the human having autosomal polycystic kidney disease.    
     
     
         82 . The method of  claim 81 , wherein the nucleic acid sequence of the PKD2 gene is determined by one or more techniques selected from the group consisting of: direct sequencing, single strand conformational analysis, restriction enzyme digestion analysis, nuclei acid probe hybridization and polymerase chain reaction.  
     
     
         83 . The method of  claim 81 , wherein the mutated PKD2 gene contains one or more deletion, insertion, point or rearrangement mutations, or a combination thereof that render the gene product encoded or expressed by the mutated gene non-functional or non-existent.  
     
     
         84 . The method of  claim 82 , wherein the nucleic acid probe comprises 12 to 40 nucleotides in length of SEQ ID NO: 6.