PKHDL1, a homolog of the autosomal recessive kidney disease gene

Abstract

Nucleic acids encoding fibrocystin-L polypeptides and fibrocystin-L polypeptides are provided. Antibodies against the polypeptides, vectors and host cells containing the nucleic acids, methods for using the nucleic acids and polypeptides, and compositions and articles of manufacture also are provided.

1 . An isolated nucleic acid comprising a sequence encoding a fibrocystin-L polypeptide. 
     
     
         2 . The isolated nucleic acid of  claim 1 , wherein said fibrocystin-L polypeptide is encoded by SEQ ID NO:1. 
     
     
         3 . The isolated nucleic acid of  claim 1 , wherein said fibrocystin-L polypeptide is encoded by SEQ ID NO:2. 
     
     
         4 . The isolated nucleic acid of  claim 1 , wherein said fibrocystin-L polypeptide comprises the amino acid sequence of SEQ ID NO:3. 
     
     
         5 . The isolated nucleic acid of  claim 1 , wherein said fibrocystin-L polypeptide comprises the amino acid sequence of SEQ ID NO:4. 
     
     
         6 . The isolated nucleic acid of  claim 1 , wherein said fibrocystin-L polypeptide comprises an amino acid sequence variant at a position selected from the group consisting of: position 702, position 1192, position 1199, position 1223, position 1514, position 1607, position 1638, position 3050, position 3607, and position 4220 of SEQ ID NO:3. 
     
     
         7 . The isolated nucleic acid of  claim 6 , wherein said amino acid sequence variant is selected from the group consisting of: Pro at position 702, Ala at position 1192, Ser at position 1199, Val at position 1223, Ser at position 1514, Ile at position 1607, Cys at position 1638, Gln at position 3050, Glu at position 3607, and Ile at position 4220. 
     
     
         8 . The isolated nucleic acid of  claim 1 , wherein said sequence comprises a sequence variant with respect to SEQ ID NO:1. 
     
     
         9 . The isolated nucleic acid of  claim 8 , wherein said sequence variant is at a position selected from the group consisting of: position 1227, position 1404, position 1920, position 1965, position 2105, position 3574, position 3599, position 3668, position 4540, position 4819, position 4913, position 6621, position 9084, position 9150, position 10821, and position 12658 of SEQ ID NO:1. 
     
     
         10 . The isolated nucleic acid of  claim 9 , wherein said sequence variant is selected from the group consisting of: A at position 1227, T at position 1404, C at position 1920, G at position 1965, C at position 2105, G at position 3574, C at position 3599, T at position 3668, A at position 4540, A at position 4819, G at position 4913, G at position 6621, T at position 9084, G at position 9150, A at position 10821, and A at position 12658. 
     
     
         11 . An isolated nucleic acid encoding a fibrocystin polypeptide, wherein said nucleic acid comprises at least 300 contiguous nucleotides of SEQ ID NO:1 or a sequence variant thereof. 
     
     
         12 . A vector comprising the isolated nucleic acid of  claim 11 . 
     
     
         13 . Host cells comprising the vector of  claim 12 . 
     
     
         14 . An isolated nucleic acid 10 to 1700 nucleotides in length, said nucleic acid comprising a sequence, said sequence comprising one or more sequence variants relative to the sequence of SEQ ID NO:1, and wherein said sequence is at least 80% identical over its length to the corresponding sequence in SEQ ID NO:1. 
     
     
         15 . The isolated nucleic acid of  claim 14 , wherein said sequence variant is at a position selected from the group consisting of: position 1227, position 1404, position 1920, position 1965, position 2105, position 3574, position 3599, position 3668, position 4540, position 4819, position 4913, position 6621, position 9084, position 9150, position 10821, and position 12658 of SEQ ID NO:1. 
     
     
         16 . A plurality of oligonucleotide primer pairs, wherein each primer is 10 to 50 nucleotides in length, and wherein each said primer pair, in the presence of mammalian genomic DNA and under polymerase chain reaction conditions, produces a nucleic acid product corresponding to a region of an PKHDL1 nucleic acid molecule, wherein said product is 30 to 1700 nucleotides in length. 
     
     
         17 . The plurality of primer pairs of  claim 16 , wherein said nucleic acid product comprises a nucleotide sequence variant relative to SEQ ID NO:1. 
     
     
         18 . The plurality of primer pairs of  claim 16 , wherein said plurality comprises at least three primer pairs. 
     
     
         19 . The plurality of primer pairs of  claim 16 , wherein said plurality comprises at least thirteen primer pairs. 
     
     
         20 . The plurality of primer pairs of  claim 16 , wherein said plurality comprises at least sixteen primer pairs. 
     
     
         21 . The plurality of primer pairs of  claim 16 , wherein said plurality comprises at least twenty-three primer pairs. 
     
     
         22 . A composition comprising a first oligonucleotide primer and a second oligonucleotide primer, wherein said first oligonucleotide primer and said second oligonucleotide primer are each 10 to 50 nucleotides in length, and wherein said first and second primers, in the presence of mammalian genomic DNA and under polymerase chain reaction conditions, produce a nucleic acid product corresponding to a region of a PKHDL1 nucleic acid molecule, wherein said product is 30 to 1700 nucleotides in length. 
     
     
         23 . The composition of  claim 22 , wherein said nucleic acid product comprises a nucleotide sequence variant relative to SEQ ID NO:1. 
     
     
         24 . An isolated nucleic acid comprising the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:2, or the complement of SEQ ID NO:1 or SEQ ID NO:2. 
     
     
         25 . An antibody having specific binding affinity for a fibrocystin-L polypeptide. 
     
     
         26 . A method for determining if a subject has altered cellular immunity, said method comprising providing a nucleic acid sample from said subject, and determining whether said nucleic acid sample contains one or more sequence variants within the PKHDL1 gene of said subject relative to a wild-type PKHDL1 gene, wherein the presence of said one or more sequence variants is associated with altered cellular immunity in said subject. 
     
     
         27 . The method of  claim 26 , wherein said nucleic acid sample is genomic DNA. 
     
     
         28 . The method of  claim 26 , wherein said determining step is performed by denaturing high performance liquid chromatography or direct sequencing. 
     
     
         29 . The method of  claim 26 , wherein said variant is at position 2105, position 3574, position 3599, position 3668, position 4540, position 4913, or position 9150 of SEQ ID NO:1. 
     
     
         30 . The method of  claim 26 , further comprising identifying said sequence variant by DNA sequencing. 
     
     
         31 . An article of manufacture comprising a substrate, wherein said substrate comprises a population of isolated nucleic acid molecules, wherein each said nucleic acid molecule is 10 to 1000 nucleotides in length, wherein each said nucleic acid molecule comprises a different nucleotide sequence variant relative to the sequence of SEQ ID NO:1, and wherein said nucleic acid molecule is at least 80% identical over its length to the corresponding sequence in SEQ ID NO:1. 
     
     
         32 . A method for monitoring the immune response of a patient after vaccination, said method comprising a) providing a biological sample from said patient after vaccination; b) determining the number of fibrocystin-L expressing T-cells in said biological sample; and c) comparing the number of fibrocystin-L expressing T-cells to a baseline number of fibrocystin-L expressing T-cells before vaccination.