Polymorphisms in the human gene for the multidrug resistance-associated protein 1 (mrp-1) and their use in diagnostic and therapeutic applications

Abstract

The present invention relates to a polymorphic MRP-1 polynucleotide, genes or vectors comprising the polynucleotides and a host cell genetically engineered with the polynucleotide or gene. Also provided are methods for producing molecular variant polypeptides, cells capable of expressing a molecular variant polypeptide and a polypeptide encoded by the polynucleotide or the gene or obtainable by the method or cells produced herein. Also provided is an antibody to the polypeptide, a transgenic animal, and a solid support comprising one or a plurality of the provided polynucleotides, genes, vectors, polypeptides, antibodies or host cells. Furthermore, methods of identifying a polymorphism, identifying and obtaining a pro-drug or drug or an inhibitor are also provided. In addition, the invention relates to methods for producing a pharmaceutical composition, diagnosing a disease and detection of the polynucleotide. Furthermore, provided herein are uses of the polynucleotides, genes, vectors, polypeptides or antibodies herein.

1 . A polynucleotide comprising a polynucleotide selected from the group consisting of: (a) a polynucleotide having the nucleic acid sequence of SEQ ID NO: 75, 76, 81, 82, 87, 88, 93, 94, 99, 100, 105, 106, 111, 112, 117, 118, 123, 124, 129, 130, 135, 136, 141, 142, 147, 148, 153, 154, 159, 160, 165, 166, 171, 172, 177, 178, 183, 184, 189, 190, 195, 196, 201, 202, 207, 208, 213, 214, 219, 220, 225, 226, 231, 232, 237, 238, 243, 244, 249, 250, 255, 256, 261, 262, 267, 268, 273, 274, 279, 280, 285, 286, 291, 292, 297, 298, 303, 304, 309, 310, 315, 316, 321, 322, 329, 330, 333, 334, 337, 338, 341, 342, 345, 346, 349, 350, 353, 354, 357, 358, 361, 362, 365, 366, 369, 370, 373, 374, 377, 378, 381, 382, 385, 386, 389, 390, 393, 394, 397 or 398; (b) a polynucleotide encoding a polypeptide having the amino acid sequence of SEQ ID NO: 324, 326, 328, 401 or 403; (c) a polynucleotide capable of hybridizing to a MRP-1 gene, wherein said polynucleotide is having a substitution or deletion of at least one nucleotide at a position corresponding to position 124667 of the MRP-1 gene (Accession No: AC 026452 ), 1884, 1720 to 1723, 1163, 926, 437, 381, 233, 189, 440 or 1625 of the MRP-1 gene (Accession No: U07050), 39508 of the MRP-1 gene (GI No: 7209451), 79, 88 or 249 of the MRP-1 gene (Accession No: AF022830), 95 or 259 of the MRP-1 gene (Accession No: AF022831), 57998, 57853 or 53282 of the MRP-1 gene (GI No: 7209451), 1377.10, 137667, 38646 or 137647 of the MRP-1 gene (Accession No: AC 026452 ), 27159, 27258, 34206 to 34207, 34218, 34215, 55156 or 55472 of the MRP-1 gene (Accession No: AC003026), 14008, 17970, 18195, 21133, 18067, 17900 of the MRP-1 gene (Accession No: U91318), or 150727 or 33551 of the MRP-1 gene (Accession No: AC 025277 ), 174 of the MRP-1 gene (Accession No: AF022828), 248 or 258 of the MRP-1 gene (Accession No: AF022829), 51798 or 50892 of the MRP-1 gene (Accession No: GI 3582311), 37971 of the MRP-1 gene (Accession No: GI 7363401), 55296, 55132, 55114, 55112 or 20097 to 20099 of the MRP-1 gene (Accession No: GI 2815549), 109 to 122, 76 to 78, 73 to 78, 70 to 78, 67 to 78 or 58 to 78 of the MRP-1 gene (Accession No: GI 4826837), 60357, 61786 or 39541 of the MRP-1 gene (Accession No: GI 7209451) or a insertion of at least one nucleotide at a position corresponding to position 55156/55157 of the MRP-1 gene (Accession No: AC003026) or 437/438 or 926/927 of the MRP-1 gene (Accession No: U07050) or 76437/76438 of the MRP-1 gene (Accession No: GI 7209451); (d) a polynucleotide capable of hybridizing to a MRP-1 gene, wherein said polynucleotide is having at a position corresponding to position 124667 of the MRP-1 gene (Accession No: AC 026452 ) a C, at a position corresponding to position 1884 of the MRP-1 gene (Accession No: U07050) a A, at a position corresponding to position 1720 to 1723 of the MRP-1 gene (Accession No: U07050) a deletion, at a position corresponding to position 1163 of the MRP-1 gene (Accession No: U07050) a T, at a position corresponding to position 926/927 of the MRP-1 gene (Accession No: U07050) a insertion, at a position corresponding to position 437/438 of the MRP-1 gene (Accession No: U07050) a insertion, at a position corresponding to position 381 of the MRP-1 gene (Accession No: U07050) a G, at a position corresponding to position 233 of the MRP-1 gene (Accession No: U07050) an A, at a position corresponding to position 189 of the MRP-1 gene (Accession No: U07050) an A, at a position corresponding to position 39508 of the MRP-1 gene (GI No: 7209451) an A, at a position corresponding to position 174 of the MRP-1 gene (Accession No: AF022828) a T, at a position corresponding to position 248 of the MRP-1 gene (Accession No: AF022829) an A, at a position corresponding to position 258 of the MRP-1 gene (Accession No: AF022829) a G, at a position corresponding to position 79 of the MRP-1 gene (Accession No: AF022830) an A, at a position corresponding to position 88 of the MRP-1 gene (Accession No: AF022830) a C, at a position corresponding to position 249 of the MRP-1 gene (Accession No: AF022830) a G, at a position corresponding to position 95 of the MRP-1 gene (Accession No: AF022831) a C, at a position corresponding to position 259 of the MRP-1 gene (Accession No: AF022831) a G, at a position corresponding to position 57998 of the MRP-1 gene (GI No: 7209451) a T, at a position corresponding to position 57853 of the MRP-1 gene (GI No: 7209451) a T, at a position corresponding to position 53282 of the MRP-1 gene (GI No: 7209451) a G, at a position corresponding to position 137710 of the MRP-1 gene (Accession No: AC 026452 ) a G, at a position corresponding to position 137667 of the MRP-1 gene (Accession No: AC 026452 ) a T, at a position corresponding to position 137647 of the MRP-1 gene (Accession No: AC 026452 ) a T, at a position corresponding to position 27159 of the MRP-1 gene (Accession No: AC003026) a C, at a position corresponding to position 27258 of the MRP-1 gene (Accession No: AC003026) an A, at a position corresponding to position 34206 to 34207 of the MRP-1 gene (Accession No: AC003026) a deletion, at a position corresponding to position 34215 of the MRP-1 gene (Accession No: AC003026) a C, at a position corresponding to position 55156/55157 of the MRP-1 gene (Accession No: AC003026) a insertion, at a position corresponding to position 55472 of the MRP-1 gene (Accession No: AC003026) a C, at a position corresponding to position 14008 of the MRP-1 gene (Accession No: U91318) an A, at a position corresponding to position 150727 of the MRP-1 gene (Accession No: AC 025277 ) an A, at a position corresponding to position 17970 of the MRP-1 gene (Accession No: U91318) a deletion, at a position corresponding to position 18195 of the MRP-1 gene (Accession No: U91318) an A, at a position corresponding to position 21133 of the MRP-1 gene (Accession No: U91318) an A, at a position corresponding to position 34218 of the MRP-1 gene (Accession No: AC003026) an A, at a position corresponding to position 18067 of the MRP-1 gene (Accession No: U91318) a T, at a position corresponding to position 440 of the MRP-1 gene (Accession No: U07050) a T, at a position corresponding to position 1625 of the MRP-1 gene (Accession No: U07050) an A, at a position corresponding to position 17900 of the MRP-1 gene (Accession No: U91318) a T, at a position corresponding to position 38646 of the MRP-1 gene (Accession No: AC 026452 ) a C, at a position corresponding to position 33551 of the MRP-1 gene (Accession No: AC 025277 ) an A, at a position corresponding to position 51798 of the MRP-1 gene (Accession No: 3582311) an G, at a position corresponding to position 37971 of the MRP-1 gene (Accession No: 7363401) an A, at a position corresponding to position 50892 of the MRP-1 gene (Accession No: 358231.1) an A, at a position corresponding to position 55296 of the MRP-1 gene (Accession No: 2815549) an A, at a position corresponding to position 55132 of the MRP-1 gene (Accession No: 2815549) an A, at a position corresponding to position 55114 of the MRP-1 gene (Accession No: 2815549) an G, at a position corresponding to position 55112 of the MRP-1 gene (Accession No: 2815549) an G, at a position corresponding to position 109 to 122 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 76 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 73 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 70 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 67 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 58 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 20097 to 20099 of the MRP-1 gene (Accession No: 2815549) deletions, at a position corresponding to position 60357 of the MRP-1 gene (Accession No: 7209451) a T, at a position corresponding to position 61786 of the MRP-1 gene (Accession No: 7209451) an A, at a position corresponding to position 76437/76438 of the MRP-1 gene (Accession No: 7209451) an insertion or at a position corresponding to position 39541 of the MRP-1 gene (Accession No: 7209451) an A; (e) a polynucleotide encoding an MRP-1 polypeptide or fragment thereof, wherein said polypeptide comprises an amino acid substitution at position 329, 433 or 723 of the MRP-1 polypeptide (Accession No: P33527) or 73 or 989 of the MRP-1 polypeptide (Accession No: GI 2828206); and (f) a polynucleotide encoding an MRP-1 polypeptide or fragment thereof, wherein said polypeptide comprises an amino acid substitution of Phe to Cys at position 329, Arg to Ser at position 433 or Arg to Gln at position 723 of the MRP-1 polypeptide (Accession No: P33527) or Thr to 11e at position 73 or Ala to Thr at position 989 of the MRP-1 polypeptide (Accession No: GI 2828206). 
     
     
         2 . The polynucleotide of  claim 1 , wherein said polynucleotide is associated with a disease selected from the group consisting of cancer diseases and multidrug resistance related diseases. 
     
     
         3 - 5 . (canceled) 
     
     
         6 . A vector comprising a polynucleotide of  claim 1 . 
     
     
         7 . (canceled) 
     
     
         8 . A host cell genetically engineered with the polynucleotide of  claim 1 . 
     
     
         9 . A method for producing a molecular variant MRP-1 polypeptide or fragment thereof comprising (a) culturing the host cell of  claim 8 ; and (b) recovering said protein or fragment from the culture. 
     
     
         10 . (canceled) 
     
     
         11 . A polypeptide or fragment thereof encoded by a polynucleotide comprising a polynucleotide selected from the group consisting of: (a) a polynucleotide having the nucleic acid sequence of SEQ ID NO: 75, 76, 81, 82, 87, 88, 93, 94, 99, 100, 105, 106, 111, 112, 117, 118, 123, 124, 129, 130, 135, 136, 141, 142, 147, 148, 153, 154, 159, 160, 165, 166, 171, 172, 177, 178, 183, 184, 189, 190, 195, 196, 201, 202, 207, 208, 213, 214, 219, 220, 225, 226, 231, 232, 237, 238, 243, 244, 249, 250, 255, 256, 261, 262, 267, 268, 273, 274, 279, 280, 285, 286, 291, 292, 297, 298, 303, 304, 309, 310, 315, 316, 321, 322, 329, 330, 333, 334, 337, 338, 341, 342, 345, 346, 349, 350, 353, 354, 357, 358, 361, 362, 365, 366, 369, 370, 373, 374, 377, 378, 381, 382, 385, 386, 389, 390, 393, 394, 397 or 398; (b) a polynucleotide encoding a polypeptide having the amino acid sequence of SEQ ID NO: 324, 326, 328, 401 or 403; (c) a polynucleotide capable of hybridizing to a MRP-1 gene, wherein said polynucleotide is having a substitution or deletion of at least one nucleotide at a position corresponding to position 124667 of the MRP-1 gene (Accession No: AC 026452 ), 1884, 1720 to 1723, 1163, 926, 437, 381, 233, 189, 440 or 1625 of the MRP-1 gene (Accession No: U07050), 39508 of the MRP-1 gene (GI No: 7209451), 79, 88 or 249 of the MRP-1 gene (Accession No: AF022830), 95 or 259 of the MRP-1 gene (Accession No: AF022831), 57998, 57853 or 53282 of the MRP-1 gene (GI No: 7209451), 1377.10, 137667, 38646 or 137647 of the MRP-1 gene (Accession No: AC 026452 ), 27159, 27258, 34206 to 34207, 34218, 34215, 55156 or 55472 of the MRP-1 gene (Accession No: AC003026), 14008, 17970, 18195, 21133, 18067, 17900 of the MRP-1 gene (Accession No: U91318), or 150727 or 33551 of the MRP-1 gene (Accession No: AC 025277 ), 174 of the MRP-1 gene (Accession No: AF022828), 248 or 258 of the MRP-1 gene (Accession No: AF022829), 51798 or 50892 of the MRP-1 gene (Accession No: GI 3582311), 37971 of the MRP-1 gene (Accession No: GI 7363401), 55296, 55132, 55114, 55112 or 20097 to 20099 of the MRP-1 gene (Accession No: GI 2815549), 109 to 122, 76 to 78, 73 to 78, 70 to 78, 67 to 78 or 58 to 78 of the MRP-1 gene (Accession No: GI 4826837), 60357, 61786 or 39541 of the MRP-1 gene (Accession No: GI 7209451) or a insertion of at least one nucleotide at a position corresponding to position 55156/55157 of the MRP-1 gene (Accession No: AC003026) or 437/438 or 926/927 of the MRP-1 gene (Accession No: U07050) or 76437/76438 of the MRP-1 gene (Accession No: GI 7209451); (d) a polynucleotide capable of hybridizing to a MRP-1 gene, wherein said polynucleotide is having at a position corresponding to position 124667 of the MRP-1 gene (Accession No: AC 026452 ) a C, at a position corresponding to position 1884 of the MRP-1 gene (Accession No: U07050) a A, at a position corresponding to position 1720 to 1723 of the MRP-1 gene (Accession No: U07050) a deletion, at a position corresponding to position 1163 of the MRP-1 gene (Accession No: U07050) a T, at a position corresponding to position 926/927 of the MRP-1 gene (Accession No: U07050) a insertion, at a position corresponding to position 437/438 of the MRP-1 gene (Accession No: U07050) a insertion, at a position corresponding to position 381 of the MRP-1 gene (Accession No: U07050) a G, at a position corresponding to position 233 of the MRP-1 gene (Accession No: U07050) an A, at a position corresponding to position 189 of the MRP-1 gene (Accession No: U07050) an A, at a position corresponding to position 39508 of the MRP-1 gene (GI No: 7209451) an A, at a position corresponding to position 174 of the MRP-1 gene (Accession No: AF022828) a T, at a position corresponding to position 248 of the MRP-1 gene (Accession No: AF022829) an A, at a position corresponding to position 258 of the MRP-1 gene (Accession No: AF022829) a G, at a position corresponding to position 79 of the MRP-1 gene (Accession No: AF022830) an A, at a position corresponding to position 88 of the MRP-1 gene (Accession No: AF022830) a C, at a position corresponding to position 249 of the MRP-1 gene (Accession No: AF022830) a G, at a position corresponding to position 95 of the MRP-1 gene (Accession No: AF022831) a C, at a position corresponding to position 259 of the MRP-1 gene (Accession No: AF022831) a G, at a position corresponding to position 57998 of the MRP-1 gene (GI No: 7209451) a T, at a position corresponding to position 57853 of the MRP-1 gene (GI No: 7209451) a T, at a position corresponding to position 53282 of the MRP-1 gene (GI No: 7209451) a G, at a position corresponding to position 137710 of the MRP-1 gene (Accession No: AC 026452 ) a G, at a position corresponding to position 137667 of the MRP-1 gene (Accession No: AC 026452 ) a T, at a position corresponding to position 137647 of the MRP-1 gene (Accession No: AC 026452 ) a T, at a position corresponding to position 27159 of the MRP-1 gene (Accession No: AC003026) a C, at a position corresponding to position 27258 of the MRP-1 gene (Accession No: AC003026) an A, at a position corresponding to position 34206 to 34207 of the MRP-1 gene (Accession No: AC003026) a deletion, at a position corresponding to position 34215 of the MRP-1 gene (Accession No: AC003026) a C, at a position corresponding to position 55156/55157 of the MRP-1 gene (Accession No: AC003026) a insertion, at a position corresponding to position 55472 of the MRP-1 gene (Accession No: AC003026) a C, at a position corresponding to position 14008 of the MRP-1 gene (Accession No: U91318) an A, at a position corresponding to position 150727 of the MRP-1 gene (Accession No: AC 025277 ) an A, at a position corresponding to position 17970 of the MRP-1 gene (Accession No: U91318) a deletion, at a position corresponding to position 18195 of the MRP-1 gene (Accession No: U91318) an A, at a position corresponding to position 21133 of the MRP-1 gene (Accession No: U91318) an A, at a position corresponding to position 34218 of the MRP-1 gene (Accession No: AC003026) an A, at a position corresponding to position 18067 of the MRP-1 gene (Accession No: U91318) a T, at a position corresponding to position 440 of the MRP-1 gene (Accession No: U07050) a T, at a position corresponding to position 1625 of the MRP-1 gene (Accession No: U07050) an A, at a position corresponding to position 17900 of the MRP-1 gene (Accession No: U91318) a T, at a position corresponding to position 38646 of the MRP-1 gene (Accession No: AC 026452 ) a C, at a position corresponding to position 33551 of the MRP-1 gene (Accession No: AC 025277 ) an A, at a position corresponding to position 51798 of the MRP-1 gene (Accession No: 3582311) an G, at a position corresponding to position 37971 of the MRP-1 gene (Accession No: 7363401) an A, at a position corresponding to position 50892 of the MRP-1 gene (Accession No: 358231.1) an A, at a position corresponding to position 55296 of the MRP-1 gene (Accession No: 2815549) an A, at a position corresponding to position 55132 of the MRP-1 gene (Accession No: 2815549) an A, at a position corresponding to position 55114 of the MRP-1 gene (Accession No: 2815549) an G, at a position corresponding to position 55112 of the MRP-1 gene (Accession No: 2815549) an G, at a position corresponding to position 109 to 122 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 76 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 73 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 70 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 67 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 58 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 20097 to 20099 of the MRP-1 gene (Accession No: 2815549) deletions, at a position corresponding to position 60357 of the MRP-1 gene (Accession No: 7209451) a T, at a position corresponding to position 61786 of the MRP-1 gene (Accession No: 7209451) an A, at a position corresponding to position 76437/76438 of the MRP-1 gene (Accession No: 7209451) an insertion or at a position corresponding to position 39541 of the MRP-1 gene (Accession No: 7209451) an A; (e) a polynucleotide encoding an MRP-1 polypeptide or fragment thereof, wherein said polypeptide comprises an amino acid substitution at position 329, 433 or 723 of the MRP-1 polypeptide (Accession No: P33527) or 73 or 989 of the MRP-1 polypeptide (Accession No: GI 2828206); and (f) a polynucleotide encoding an MRP-1 polypeptide or fragment thereof, wherein said polypeptide comprises an amino acid substitution of Phe to Cys at position 329, Arg to Ser at position 433 or Arg to Gln at position 723 of the MRP-1 polypeptide (Accession No: P33527) or Thr to 11e at position 73 or Ala to Thr at position 989 of the MRP-1 polypeptide (Accession No: GI 2828206). 
     
     
         12 - 16 . (canceled) 
     
     
         17 . A solid support comprising one or a plurality of the polynucleotide of  claim 1 . 
     
     
         18 - 28 . (canceled) 
     
     
         29 . A method of diagnosing a disorder related to the presence of a molecular variant of a MRP-1 gene or susceptibility to such a disorder comprising determining the presence of a polynucleotide comprising a polynucleotide selected from the group consisting of: (a) a polynucleotide having the nucleic acid sequence of SEQ ID NO: 75, 76, 81, 82, 87, 88, 93, 94, 99, 100, 105, 106, 111, 112, 117, 118, 123, 124, 129, 130, 135, 136, 141, 142, 147, 148, 153, 154, 159, 160, 165, 166, 171, 172, 177, 178, 183, 184, 189, 190, 195, 196, 201, 202, 207, 208, 213, 214, 219, 220, 225, 226, 231, 232, 237, 238, 243, 244, 249, 250, 255, 256, 261, 262, 267, 268, 273, 274, 279, 280, 285, 286, 291, 292, 297, 298, 303, 304, 309, 310, 315, 316, 321, 322, 329, 330, 333, 334, 337, 338, 341, 342, 345, 346, 349, 350, 353, 354, 357, 358, 361, 362, 365, 366, 369, 370, 373, 374, 377, 378, 381, 382, 385, 386, 389, 390, 393, 394, 397 or 398; (b) a polynucleotide encoding a polypeptide having the amino acid sequence of SEQ ID NO: 324, 326, 328, 401 or 403; (c) a polynucleotide capable of hybridizing to a MRP-1 gene, wherein said polynucleotide is having a substitution or deletion of at least one nucleotide at a position corresponding to position 124667 of the MRP-1 gene (Accession No: AC 026452 ), 1884, 1720 to 1723, 1163, 926, 437, 381, 233, 189, 440 or 1625 of the MRP-1 gene (Accession No: U07050), 39508 of the MRP-1 gene (GI No: 7209451), 79, 88 or 249 of the MRP-1 gene (Accession No: AF022830), 95 or 259 of the MRP-1 gene (Accession No: AF022831), 57998, 57853 or 53282 of the MRP-1 gene (GI No: 7209451), 1377.10, 137667, 38646 or 137647 of the MRP-1 gene (Accession No: AC 026452 ), 27159, 27258, 34206 to 34207, 34218, 34215, 55156 or 55472 of the MRP-1 gene (Accession No: AC003026), 14008, 17970, 18195, 21133, 18067, 17900 of the MRP-1 gene (Accession No: U91318), or 150727 or 33551 of the MRP-1 gene (Accession No: AC 025277 ), 174 of the MRP-1 gene (Accession No: AF022828), 248 or 258 of the MRP-1 gene (Accession No: AF022829), 51798 or 50892 of the MRP-1 gene (Accession No: GI 3582311), 37971 of the MRP-1 gene (Accession No: GI 7363401), 55296, 55132, 55114, 55112 or 20097 to 20099 of the MRP-1 gene (Accession No: GI 2815549), 109 to 122, 76 to 78, 73 to 78, 70 to 78, 67 to 78 or 58 to 78 of the MRP-1 gene (Accession No: GI 4826837), 60357, 61786 or 39541 of the MRP-1 gene (Accession No: GI 7209451) or a insertion of at least one nucleotide at a position corresponding to position 55156/55157 of the MRP-1 gene (Accession No: AC003026) or 437/438 or 926/927 of the MRP-1 gene (Accession No: U07050) or 76437/76438 of the MRP-1 gene (Accession No: GI 7209451); (d) a polynucleotide capable of hybridizing to a MRP-1 gene, wherein said polynucleotide is having at a position corresponding to position 124667 of the MRP-1 gene (Accession No: AC 026452 ) a C, at a position corresponding to position 1884 of the MRP-1 gene (Accession No: U07050) a A, at a position corresponding to position 1720 to 1723 of the MRP-1 gene (Accession No: U07050) a deletion, at a position corresponding to position 1163 of the MRP-1 gene (Accession No: U07050) a T, at a position corresponding to position 926/927 of the MRP-1 gene (Accession No: U07050) a insertion, at a position corresponding to position 437/438 of the MRP-1 gene (Accession No: U07050) a insertion, at a position corresponding to position 381 of the MRP-1 gene (Accession No: U07050) a G, at a position corresponding to position 233 of the MRP-1 gene (Accession No: U07050) an A, at a position corresponding to position 189 of the MRP-1 gene (Accession No: U07050) an A, at a position corresponding to position 39508 of the MRP-1 gene (GI No: 7209451) an A, at a position corresponding to position 174 of the MRP-1 gene (Accession No: AF022828) a T, at a position corresponding to position 248 of the MRP-1 gene (Accession No: AF022829) an A, at a position corresponding to position 258 of the MRP-1 gene (Accession No: AF022829) a G, at a position corresponding to position 79 of the MRP-1 gene (Accession No: AF022830) an A, at a position corresponding to position 88 of the MRP-1 gene (Accession No: AF022830) a C, at a position corresponding to position 249 of the MRP-1 gene (Accession No: AF022830) a G, at a position corresponding to position 95 of the MRP-1 gene (Accession No: AF022831) a C, at a position corresponding to position 259 of the MRP-1 gene (Accession No: AF022831) a G, at a position corresponding to position 57998 of the MRP-1 gene (GI No: 7209451) a T, at a position corresponding to position 57853 of the MRP-1 gene (GI No: 7209451) a T, at a position corresponding to position 53282 of the MRP-1 gene (GI No: 7209451) a G, at a position corresponding to position 137710 of the MRP-1 gene (Accession No: AC 026452 ) a G, at a position corresponding to position 137667 of the MRP-1 gene (Accession No: AC 026452 ) a T, at a position corresponding to position 137647 of the MRP-1 gene (Accession No: AC 026452 ) a T, at a position corresponding to position 27159 of the MRP-1 gene (Accession No: AC003026) a C, at a position corresponding to position 27258 of the MRP-1 gene (Accession No: AC003026) an A, at a position corresponding to position 34206 to 34207 of the MRP-1 gene (Accession No: AC003026) a deletion, at a position corresponding to position 34215 of the MRP-1 gene (Accession No: AC003026) a C, at a position corresponding to position 55156/55157 of the MRP-1 gene (Accession No: AC003026) a insertion, at a position corresponding to position 55472 of the MRP-1 gene (Accession No: AC003026) a C, at a position corresponding to position 14008 of the MRP-1 gene (Accession No: U91318) an A, at a position corresponding to position 150727 of the MRP-1 gene (Accession No: AC 025277 ) an A, at a position corresponding to position 17970 of the MRP-1 gene (Accession No: U91318) a deletion, at a position corresponding to position 18195 of the MRP-1 gene (Accession No: U91318) an A, at a position corresponding to position 21133 of the MRP-1 gene (Accession No: U91318) an A, at a position corresponding to position 34218 of the MRP-1 gene (Accession No: AC003026) an A, at a position corresponding to position 18067 of the MRP-1 gene (Accession No: U91318) a T, at a position corresponding to position 440 of the MRP-1 gene (Accession No: U07050) a T, at a position corresponding to position 1625 of the MRP-1 gene (Accession No: U07050) an A, at a position corresponding to position 17900 of the MRP-1 gene (Accession No: U91318) a T, at a position corresponding to position 38646 of the MRP-1 gene (Accession No: AC 026452 ) a C, at a position corresponding to position 33551 of the MRP-1 gene (Accession No: AC 025277 ) an A, at a position corresponding to position 51798 of the MRP-1 gene (Accession No: 3582311) an G, at a position corresponding to position 37971 of the MRP-1 gene (Accession No: 7363401) an A, at a position corresponding to position 50892 of the MRP-1 gene (Accession No: 358231.1) an A, at a position corresponding to position 55296 of the MRP-1 gene (Accession No: 2815549) an A, at a position corresponding to position 55132 of the MRP-1 gene (Accession No: 2815549) an A, at a position corresponding to position 55114 of the MRP-1 gene (Accession No: 2815549) an G, at a position corresponding to position 55112 of the MRP-1 gene (Accession No: 2815549) an G, at a position corresponding to position 109 to 122 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 76 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 73 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 70 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 67 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 58 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 20097 to 20099 of the MRP-1 gene (Accession No: 2815549) deletions, at a position corresponding to position 60357 of the MRP-1 gene (Accession No: 7209451) a T, at a position corresponding to position 61786 of the MRP-1 gene (Accession No: 7209451) an A, at a position corresponding to position 76437/76438 of the MRP-1 gene (Accession No: 7209451) an insertion or at a position corresponding to position 39541 of the MRP-1 gene (Accession No: 7209451) an A; (e) a polynucleotide encoding an MRP-1 polypeptide or fragment thereof, wherein said polypeptide comprises an amino acid substitution at position 329, 433 or 723 of the MRP-1 polypeptide (Accession No: P33527) or 73 or 989 of the MRP-1 polypeptide (Accession No: GI 2828206); and (f) a polynucleotide encoding an MRP-1 polypeptide or fragment thereof, wherein said polypeptide comprises an amino acid substitution of Phe to Cys at position 329, Arg to Ser at position 433 or Arg to Gln at position 723 of the MRP-1 polypeptide (Accession No: P33527) or Thr to 11e at position 73 or Ala to Thr at position 989 of the MRP-1 polypeptide (Accession No: GI 2828206); or a polypeptide encoded by the polynucleotide in a sample from a subject. 
     
     
         30 - 31 . (canceled) 
     
     
         32 . The method of  claim 29 , wherein said disorder is a cancer disease or a disease related to multidrug resistance. 
     
     
         33 . (canceled) 
     
     
         34 . A method of detection of the polynucleotide of  claim 1  in a sample comprising the steps of
 (a) contacting a solid support comprising one or a plurality of the polynucleotide of  claim 1  with the sample under conditions allowing interaction of the polynucleotide of  claim 1  with the immobilized targets on a solid support and; 
 (b) determining the binding of said polynucleotide or said gene to said immobilized targets on a solid support. 
 
     
     
         35 . An in vitro method for diagnosing a disease comprising the steps of
 (a) contacting a solid support comprising one or a plurality of a polynucleotide with a sample under conditions allowing interaction of the polynucleotide with the immobilized targets on a solid support and;   (b) determining the binding of said polynucleotide or said gene to said immobilized targets on a solid support, wherein binding of said polynucleotide or gene to said immobilized targets on said solid support is indicative for the presence or the absence of said disease or a prevalence for said disease; wherein the polynucleotide comprises a polynucleotide selected from the group consisting of: (a) a polynucleotide having the nucleic acid sequence of SEQ ID NO: 75, 76, 81, 82, 87, 88, 93, 94, 99, 100, 105, 106, 111, 112, 117, 118, 123, 124, 129, 130, 135, 136, 141, 142, 147, 148, 153, 154, 159, 160, 165, 166, 171, 172, 177, 178, 183, 184, 189, 190, 195, 196, 201, 202, 207, 208, 213, 214, 219, 220, 225, 226, 231, 232, 237, 238, 243, 244, 249, 250, 255, 256, 261, 262, 267, 268, 273, 274, 279, 280, 285, 286, 291, 292, 297, 298, 303, 304, 309, 310, 315, 316, 321, 322, 329, 330, 333, 334, 337, 338, 341, 342, 345, 346, 349, 350, 353, 354, 357, 358, 361, 362, 365, 366, 369, 370, 373, 374, 377, 378, 381, 382, 385, 386, 389, 390, 393, 394, 397 or 398; (b) a polynucleotide encoding a polypeptide having the amino acid sequence of SEQ ID NO: 324, 326, 328, 401 or 403; (c) a polynucleotide capable of hybridizing to a MRP-1 gene, wherein said polynucleotide is having a substitution or deletion of at least one nucleotide at a position corresponding to position 124667 of the MRP-1 gene (Accession No: AC 026452 ), 1884, 1720 to 1723, 1163, 926, 437, 381, 233, 189, 440 or 1625 of the MRP-1 gene (Accession No: U07050), 39508 of the MRP-1 gene (GI No: 7209451), 79, 88 or 249 of the MRP-1 gene (Accession No: AF022830), 95 or 259 of the MRP-1 gene (Accession No: AF022831), 57998, 57853 or 53282 of the MRP-1 gene (GI No: 7209451), 1377.10, 137667, 38646 or 137647 of the MRP-1 gene (Accession No: AC 026452 ), 27159, 27258, 34206 to 34207, 34218, 34215, 55156 or 55472 of the MRP-1 gene (Accession No: AC003026), 14008, 17970, 18195, 21133, 18067, 17900 of the MRP-1 gene (Accession No: U91318), or 150727 or 33551 of the MRP-1 gene (Accession No: AC 025277 ), 174 of the MRP-1 gene (Accession No: AF022828), 248 or 258 of the MRP-1 gene (Accession No: AF022829), 51798 or 50892 of the MRP-1 gene (Accession No: GI 3582311), 37971 of the MRP-1 gene (Accession No: GI 7363401), 55296, 55132, 55114, 55112 or 20097 to 20099 of the MRP-1 gene (Accession No: GI 2815549), 109 to 122, 76 to 78, 73 to 78, 70 to 78, 67 to 78 or 58 to 78 of the MRP-1 gene (Accession No: GI 4826837), 60357, 61786 or 39541 of the MRP-1 gene (Accession No: GI 7209451) or a insertion of at least one nucleotide at a position corresponding to position 55156/55157 of the MRP-1 gene (Accession No: AC003026) or 437/438 or 926/927 of the MRP-1 gene (Accession No: U07050) or 76437/76438 of the MRP-1 gene (Accession No: GI 7209451); (d) a polynucleotide capable of hybridizing to a MRP-1 gene, wherein said polynucleotide is having at a position corresponding to position 124667 of the MRP-1 gene (Accession No: AC 026452 ) a C, at a position corresponding to position 1884 of the MRP-1 gene (Accession No: U07050) a A, at a position corresponding to position 1720 to 1723 of the MRP-1 gene (Accession No: U07050) a deletion, at a position corresponding to position 1163 of the MRP-1 gene (Accession No: U07050) a T, at a position corresponding to position 926/927 of the MRP-1 gene (Accession No: U07050) a insertion, at a position corresponding to position 437/438 of the MRP-1 gene (Accession No: U07050) a insertion, at a position corresponding to position 381 of the MRP-1 gene (Accession No: U07050) a G, at a position corresponding to position 233 of the MRP-1 gene (Accession No: U07050) an A, at a position corresponding to position 189 of the MRP-1 gene (Accession No: U07050) an A, at a position corresponding to position 39508 of the MRP-1 gene (GI No: 7209451) an A, at a position corresponding to position 174 of the MRP-1 gene (Accession No: AF022828) a T, at a position corresponding to position 248 of the MRP-1 gene (Accession No: AF022829) an A, at a position corresponding to position 258 of the MRP-1 gene (Accession No: AF022829) a G, at a position corresponding to position 79 of the MRP-1 gene (Accession No: AF022830) an A, at a position corresponding to position 88 of the MRP-1 gene (Accession No: AF022830) a C, at a position corresponding to position 249 of the MRP-1 gene (Accession No: AF022830) a G, at a position corresponding to position 95 of the MRP-1 gene (Accession No: AF022831) a C, at a position corresponding to position 259 of the MRP-1 gene (Accession No: AF022831) a G, at a position corresponding to position 57998 of the MRP-1 gene (GI No: 7209451) a T, at a position corresponding to position 57853 of the MRP-1 gene (GI No: 7209451) a T, at a position corresponding to position 53282 of the MRP-1 gene (GI No: 7209451) a G, at a position corresponding to position 137710 of the MRP-1 gene (Accession No: AC 026452 ) a G, at a position corresponding to position 137667 of the MRP-1 gene (Accession No: AC 026452 ) a T, at a position corresponding to position 137647 of the MRP-1 gene (Accession No: AC 026452 ) a T, at a position corresponding to position 27159 of the MRP-1 gene (Accession No: AC003026) a C, at a position corresponding to position 27258 of the MRP-1 gene (Accession No: AC003026) an A, at a position corresponding to position 34206 to 34207 of the MRP-1 gene (Accession No: AC003026) a deletion, at a position corresponding to position 34215 of the MRP-1 gene (Accession No: AC003026) a C, at a position corresponding to position 55156/55157 of the MRP-1 gene (Accession No: AC003026) a insertion, at a position corresponding to position 55472 of the MRP-1 gene (Accession No: AC003026) a C, at a position corresponding to position 14008 of the MRP-1 gene (Accession No: U91318) an A, at a position corresponding to position 150727 of the MRP-1 gene (Accession No: AC 025277 ) an A, at a position corresponding to position 17970 of the MRP-1 gene (Accession No: U91318) a deletion, at a position corresponding to position 18195 of the MRP-1 gene (Accession No: U91318) an A, at a position corresponding to position 21133 of the MRP-1 gene (Accession No: U91318) an A, at a position corresponding to position 34218 of the MRP-1 gene (Accession No: AC003026) an A, at a position corresponding to position 18067 of the MRP-1 gene (Accession No: U91318) a T, at a position corresponding to position 440 of the MRP-1 gene (Accession No: U07050) a T, at a position corresponding to position 1625 of the MRP-1 gene (Accession No: U07050) an A, at a position corresponding to position 17900 of the MRP-1 gene (Accession No: U91318) a T, at a position corresponding to position 38646 of the MRP-1 gene (Accession No: AC 026452 ) a C, at a position corresponding to position 33551 of the MRP-1 gene (Accession No: AC 025277 ) an A, at a position corresponding to position 51798 of the MRP-1 gene (Accession No: 3582311) an G, at a position corresponding to position 37971 of the MRP-1 gene (Accession No: 7363401) an A, at a position corresponding to position 50892 of the MRP-1 gene (Accession No: 358231.1) an A, at a position corresponding to position 55296 of the MRP-1 gene (Accession No: 2815549) an A, at a position corresponding to position 55132 of the MRP-1 gene (Accession No: 2815549) an A, at a position corresponding to position 55114 of the MRP-1 gene (Accession No: 2815549) an G, at a position corresponding to position 55112 of the MRP-1 gene (Accession No: 2815549) an G, at a position corresponding to position 109 to 122 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 76 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 73 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 70 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 67 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 58 to 78 of the MRP-1 gene (Accession No: 4826837) deletions, at a position corresponding to position 20097 to 20099 of the MRP-1 gene (Accession No: 2815549) deletions, at a position corresponding to position 60357 of the MRP-1 gene (Accession No: 7209451) a T, at a position corresponding to position 61786 of the MRP-1 gene (Accession No: 7209451) an A, at a position corresponding to position 76437/76438 of the MRP-1 gene (Accession No: 7209451) an insertion or at a position corresponding to position 39541 of the MRP-1 gene (Accession No: 7209451) an A; (e) a polynucleotide encoding an MRP-1 polypeptide or fragment thereof, wherein said polypeptide comprises an amino acid substitution at position 329, 433 or 723 of the MRP-1 polypeptide (Accession No: P33527) or 73 or 989 of the MRP-1 polypeptide (Accession No: GI 2828206); and (f) a polynucleotide encoding an MRP-1 polypeptide or fragment thereof, wherein said polypeptide comprises an amino acid substitution of Phe to Cys at position 329, Arg to Ser at position 433 or Arg to Gln at position 723 of the MRP-1 polypeptide (Accession No: P33527) or Thr to 11e at position 73 or Ala to Thr at position 989 of the MRP-1 polypeptide (Accession No: GI 2828206).   
     
     
         36 . A diagnostic composition comprising the polynucleotide of  claim 1 . 
     
     
         37 - 41 . (canceled) 
     
     
         42 . A diagnostic kit for detection of a single nucleotide polymorphism comprising the polynucleotide of  claim 1  or the solid support comprising one or a plurality of the polynucleotide of  claim 1 .