Alstroem syndrome gene, gene variants, expressed protein and methods of diagnosis for Alstroem syndrome

Abstract

The present invention relates to a nucleic acid sequence linked to Alström syndrome, variants of that nucleic acid sequence, the protein produced by that nucleic acid sequence and screening methods for testing individuals to determine if they are carriers of Alström syndrome.

We claim:  
     
         1 . An isolated nucleic acid molecule selected from the group consisting of: 
 nucleotide sequence SEQ ID NO:NO: 1,    nucleotide sequences hybridizing to SEQ ID NO:NO: 1 or the complement of SEQ ID NO:NO: 1 under stringent hybridization conditions and    nucleotide sequences encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:NO: 2.    
     
     
         2 . The nucleic acid molecule of  claim 1 , selected from the group consisting of: 
 a nucleotide sequence comprising SEQ ID NO:NO: 1 with 19 nucleotides inserted after the 3737 th  nucleotide of SEQ ID NO:NO: 1;    a nucleotide sequence comprising SEQ ID NO:NO: 1 with the 1582 nd  nucleotide of SEQ ID NO:NO: 1 being T;    a nucleotide sequence comprising SEQ ID NO:NO: 1 with the 3808 th  nucleotide of SEQ ID NO:NO: 1 being T, the 3809 th  nucleotide of SEQ ID NO:NO: 1 being deleted and the 3813 th  nucleotide of SEQ ID NO:NO: 1 being A;    a nucleotide sequence comprising SEQ ID NO:NO: 1 with the 3974 th  nucleotide of SEQ ID NO:NO: 1 being deleted;    a nucleotide sequence comprising SEQ ID NO:NO: 1 with the 4648 th  of SEQ ID NO: 1 being T; and    a nucleotide sequence comprising SEQ ID NO: 1 with an A inserted after the 1594 th  nucleotide of SEQ ID NO: 1.    
     
     
         3 . The nucleic acid molecule of  claim 1 , further comprising vector nucleic acid sequences.  
     
     
         4 . The nucleic acid molecule which is at least about 70% identical to the entire length of the nucleic acid molecule of  claim 1 .  
     
     
         5 . The nucleic acid molecule which is at least about 80% identical to the entire length of the nucleic acid molecule of  claim 1 .  
     
     
         6 . The nucleic acid molecule which is at least about 90% identical to the entire length of the nucleic acid molecule of  claim 1 .  
     
     
         7 . The nucleic acid molecule which is at least about 95% identical to the entire length of the nucleic acid molecule of  claim 1 .  
     
     
         8 . An isolated host cell comprising a nucleic acid molecule selected from the group consisting of 
 nucleotide sequence SEQ ID NO: 1,    nucleotide sequences hybridizing to SEQ ID NO: 1 or the complement of SEQ ID NO: 1 under stringent hybridization conditions and    nucleotide sequences encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 2.    
     
     
         9 . The host cell of  claim 8  which is a mammalian host cell.  
     
     
         10 . A method for producing a polypeptide comprising culturing the host cell of  claim 8  under conditions in which the nucleic acid molecule is expressed.  
     
     
         11 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of 
 the amino acid sequence of SEQ ID NO: 2,    the amino acid sequence encoded by the nucleic acid molecule having the nucleotide sequence SEQ ID NO: 1,    the amino acid sequence encoded by the nucleic acid molecule having nucleotide sequences hybridizing to SEQ ID NO: 1 or the complement of SEQ ID NO: 1 under stringent hybridization conditions and    the amino acid sequence encoded by the nucleic acid molecule having nucleotide sequences encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 2.    
     
     
         12 . An isolated polypeptide comprising at least 50 contiguous amino acid residues of the amino acid sequence of SEQ ID NO: 2.  
     
     
         13 . An isolated polypeptide comprising at least 100 contiguous amino acid residues of the amino acid sequence of SEQ ID NO: 2.  
     
     
         14 . An isolated polypeptide comprising at least 200 contiguous amino acid residues of the amino acid sequence of SEQ ID NO: 2.  
     
     
         15 . A method of diagnosing Alström Syndrome or screening for carriers of Alström Syndrome comprising testing genetic material from a putative carrier for mutations in SEQ ID NO: 1 of ALMS1.  
     
     
         16 . A method of diagnosing Alström Syndrome in a patient, the method comprising determining the presence or absence of the protein encoded by SEQ ID NO: 1 in a tissue sample of the patient.  
     
     
         17 . The method of  claim 16 , wherein the step of determining the presence or absence of the protein encoded by SEQ ID NO: 1 is performed by adding an antibody specific for the protein encoded by SEQ ID NO: 1 to proteins from the tissue sample and determining the amount of antibody which binds to the proteins from the tissue sample.  
     
     
         18 . A method for identifying a compound suitable for treating Alström Syndrome comprising: 
 contacting a polypeptide having the amino acid sequence of SEQ ID NO: 2 or a fragment thereof, or a cell expressing a polypeptide having the amino acid sequence of SED ID NO: 2 or a fragment thereof, with a test compound; and  
 determining whether said polypeptide or fragment thereof binds to said test compound, thereby identifying a compound suitable for treating Alström Syndrome.