Claims
- 1. A method for detecting a fetal cell in a maternal blood sample, comprising the steps of:
(a) contacting said maternal blood sample with a first probe, said first probe comprising:
(i) a nucleotide sequence corresponding to SEQ ID NO: 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42, (ii) a nucleotide sequence having at least 90% sequence identity to at least 20 consecutive nucleotides of SEQ ID NO: 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42, or (iii) a nucleotide sequence having at least 80% sequence identity to at least 40 consecutive nucleotides of SEQ ID NO: 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42, which first probe selectively or specifically hybridizes to mRNA in fetal cells if present in the maternal blood sample; and (b) identifying whether or not said maternal blood sample comprises a cell that comprises mRNA that detectably hybridizes to the first probe, thereby detecting whether or not said maternal blood sample contains a fetal cell.
- 2. The method of claim 1, wherein the first probe specifically hybridizes to fetal cells.
- 3. The method of claim 1, wherein the first probe selectively hybridizes to fetal cells.
- 4. The method of claim 1 in which the first probe comprises a label.
- 5. The method of claim 4 in which the label is a radioactive label, a fluorescent label, a colorimetric reagent, or an enzyme.
- 6. The method of claim 1, wherein the nucleotide sequence is 20-30 nucleotides in length.
- 7. The method of claim 1, wherein the nucleotide sequence is 30-40 nucleotides in length.
- 8. The method of claim 1, wherein the nucleotide sequence is 40-60 nucleotides in length.
- 9. The method of claim 1, wherein the nucleotide sequence is 60-80 nucleotides in length.
- 10. The method of claim 1, wherein the nucleotide sequence is 80-100 nucleotides in length.
- 11. The method of claim 1, wherein the nucleotide sequence is 100-150 nucleotides in length.
- 12. The method of claim 1, wherein the nucleotide sequence is 150-200 nucleotides in length.
- 13. The method of claim 1, wherein the nucleotide sequence is greater than 200 nucleotides in length.
- 14. The method of claim 1, wherein the probe is less than 40 nucleotides in length.
- 15. The method of claim 1, wherein the probe is less than 50 nucleotides in length.
- 16. The method of claim 1, wherein the probe is less than 100 nucleotides in length.
- 17. The method of claim 1, wherein the probe is less than 200 nucleotides in length.
- 18. The method of claim 1, wherein the probe is less than 300 nucleotides in length.
- 19. The method of claim 1, wherein the probe is less than 400 nucleotides in length.
- 20. The method of claim 1, wherein the probe is less than 500 nucleotides in length.
- 21. The method of claim 1, wherein the probe is less than 1,000 nucleotides in length.
- 22. The method of claim 1, wherein the probe is less than 2,000 nucleotides in length.
- 23. The method of claim 1, further comprising, prior to step (b), contacting said maternal blood sample with a second probe which selectively or specifically hybridizes to fetal cells if present in the maternal blood sample.
- 24. The method of claim 23, further comprising detecting a cell in said maternal blood sample which comprises mRNA that hybridizes to the second probe.
- 25. The method of claim 24, wherein the first and second probe are labeled with the same type of label.
- 26. The method of claim 23, wherein the first and second probes correspond to the same mRNA.
- 27. The method of claim 23, wherein the first and second probes correspond to different mRNAs.
- 28. The method of claim 1, further comprising, prior to step (a), immunoenriching the maternal blood sample for fetal cells.
- 29. The method of claim 28, wherein immunoenriching the maternal blood sample comprises:
(a) contacting the maternal blood sample with an antibody that selectively or specifically binds to fetal cells in the maternal blood sample; and (b) separating cells in the maternal blood sample that bind to the antibody from cells that do not bind to the antibody, thereby immunoenriching the maternal blood sample for fetal cells.
- 30. The method of claim 28, wherein immunoenriching the maternal blood sample comprises:
(a) contacting the maternal blood sample with an antibody that selectively or specifically binds to maternal cells in the maternal blood sample; and (b) separating cells in the maternal blood sample that do not bind to the antibody from cells that bind to the antibody, thereby immunoenriching the maternal blood sample for fetal cells.
- 31. The method of claim 1, wherein the probe is an RNA probe.
- 32. The method of claim 1, wherein the probe is a DNA probe.
- 33. The method of claim 1, wherein the fetal cell is an erythroblast.
- 34. The method of claim 1, wherein the fetal cell is a trophoblast.
- 35. The method of claim 1, wherein nucleotide sequence has at least 95% sequenceidentity to at least 20 consecutive nucleotides of SEQ ID NO: 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42.
- 36. The method of claim 35, wherein nucleotide sequence has 100% sequence identity to at least 20 consecutive nucleotides of SEQ ID NO:10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42.
- 37. The method of claim 1, wherein nucleotide sequence has at least 85% sequence identity to at least 40 consecutive nucleotides of SEQ ID NO:10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42.
- 38. The method of claim 37, wherein the nucleotide sequence has at least 90% sequence identity to at least 40 consecutive nucleotides of SEQ ID NO: 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42.
- 39. The method of claim 38, wherein the nucleotide sequence has at least 95% sequence identity to at least 40 consecutive nucleotides of SEQ ID NO: 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42.
- 40. The method of claim 39, wherein the nucleotide sequence has 100% sequence identity to at least 40 consecutive nucleotides of SEQ ID NO: 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42.
- 41. A method for diagnosing an abnormality in a fetal cell, comprising the steps of:
(a) contacting a maternal blood sample with a first probe, said first probe comprising:
(i) a nucleotide sequence corresponding to SEQ ID NO: 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42, (ii) a nucleotide sequence having at least 90% sequence identity to at least 20 consecutive nucleotides of SEQ ID NO: 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42, or (iii) a nucleotide sequence having at least 80% sequence identity to at least 40 consecutive nucleotides of SEQ ID NO: 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42, which first probe selectively or specifically hybridizes to mRNA in a fetal cell if present in the maternal blood sample; (b) identifying whether or not said maternal blood sample comprises a cell that comprises mRNA that detectably hybridizes to the first probe, thereby detecting whether or not said maternal blood sample contains a fetal cell; and (c) if a fetal cell is detected, determining whether the abnormality exists in said fetal cell, thereby diagnosing the abnormality.
- 42. The method of claim 41, wherein the first probe specifically hybridizes to the fetal cell.
- 43. The method of claim 41, wherein the first probe selectively hybridizes to the fetal cell.
- 44. The method of claim 41 in which the first probe comprises a label.
- 45. The method of claim 44 in which the label is a radioactive label, a fluorescent label, a colorimetric reagent or an enzyme.
- 46. The method of claim 41, wherein the nucleotide sequence is 20-30 nucleotides in length.
- 47. The method of claim 41, wherein the nucleotide sequence is 30-40 nucleotides in length.
- 48. The method of claim 41, wherein the nucleotide sequence is 40-60 nucleotides in length.
- 49. The method of claim 41, wherein the nucleotide sequence is 60-80 nucleotides in length.
- 50. The method of claim 41, wherein the nucleotide sequence is 80-100 nucleotides in length.
- 51. The method of claim 41, wherein the nucleotide sequence is 100-150 nucleotides in length.
- 52. The method of claim 41, wherein the nucleotide sequence is 150-200 nucleotides in length.
- 53. The method of claim 41, wherein the nucleotide sequence is greater than 200 nucleotides in length.
- 54. The method of claim 41, wherein the probe is less than 40 nucleotides in length.
- 55. The method of claim 41, wherein the probe is less than 50 nucleotides in length.
- 56. The method of claim 41, wherein the probe is less than 100 nucleotides in length.
- 57. The method of claim 41, wherein the probe is less than 200 nucleotides in length.
- 58. The method of claim 41, wherein the probe is less than 300 nucleotides in length.
- 59. The method of claim 41, wherein the probe is less than 400 nucleotides in length.
- 60. The method of claim 41, wherein the probe is less than 500 nucleotides in length.
- 61. The method of claim 41, wherein the probe is less than 1,000 nucleotides in length.
- 62. The method of claim 41, wherein the probe is less than 2,000 nucleotides in length.
- 63. The method of claim 41, further comprising, prior to step (b), contacting said maternal blood sample with a second probe which selectively or specifically hybridizes to fetal cells if present in the maternal blood sample.
- 64. The method of claim 63, further comprising detecting a cell in said maternal blood sample which comprises mRNA that hybridizes to the second probe.
- 65. The method of claim 64, wherein the first and second probe are labeled with the same type of label.
- 66. The method of claim 63, wherein the first and second probes correspond to the same mRNA.
- 67. The method of claim 63, wherein the first and second probes correspond to different mRNAs.
- 68. The method of claim 41, further comprising, prior to step (a), enriching the maternal blood sample for fetal cells prior.
- 69. The method of claim 68, wherein immunoenriching the maternal blood sample comprises:
(a) contacting the maternal blood sample with an antibody that selectively or specifically binds to fetal cells in the maternal blood sample; and (b) separating cells in the maternal blood sample that bind to the antibody from cells that do not bind to the antibody, thereby immunoenriching the maternal blood sample for fetal cells.
- 70. The method of claim 68, wherein immunoenriching the maternal blood sample comprises:
(a) contacting the maternal blood sample with an antibody that selectively or specifically binds to maternal cells in the maternal blood sample; and (b) separating cells in the maternal blood sample that do not bind to the antibody from cells that bind to the antibody, thereby immunoenriching the maternal blood sample for fetal cells.
- 71. The method of claim 41, wherein the probe is an RNA probe.
- 72. The method of claim 41, wherein the probe is a DNA probe.
- 73. The method of claim 41, wherein nucleotide sequence has at least 95% sequence identity to at least 20 consecutive nucleotides of SEQ ID NO:10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42.
- 74. The method of claim 73, wherein nucleotide sequence has 100% sequence identity to at least 20 consecutive nucleotides of SEQ ID NO:10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42.
- 75. The method of claim 41, wherein nucleotide sequence has at least 85% sequence identity to at least 40 consecutive nucleotides of SEQ ID NO: 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42.
- 76. The method of claim 75, wherein the nucleotide sequence has at least 90% sequence identity to at least 40 consecutive nucleotides of SEQ ID NO: 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42.
- 77. The method of claim 76, wherein the nucleotide sequence has at least 95% sequence identity to at least 40 consecutive nucleotides of SEQ ID NO: 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42.
- 78. The method of claim 77, wherein the nucleotide sequence has 100% sequence identity to at least 40 consecutive nucleotides of SEQ ID NO:10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42.
- 79. The method of claim 41, wherein the abnormality is a chromosomal abnormality.
- 80. The method of claim 79, wherein the chromosomal abnormality is an aneuploidy.
- 81. The method of claim 80, wherein the aneuploidy is trisomy 13, trisomy 21, or Klinefelter syndrome.
- 82. The method of claim 41, wherein the abnormality is a single gene disorder.
- 83. The method of claim 82, wherein the single gene disorder is a deletion, insertion or substitution disorder.
- 84. The method of 83, wherein the single gene disorder is spina bifida, sickle-cell anemia, a thalassemia, Marfan Syndrome, Duchenne Muscular Dystrophy, or cystic fibrosis.
- 85. The method of claim 41, wherein the abnormality is a nucleotide triplet expansion in the gene.
- 86. The method of claim 85, wherein the gene is the Fragile X Syndrome gene, the Friedreich's ataxia gene, the myotonic dystrophy gene, or the Huntington's disease gene.
- 87. The method of claim 41, wherein the fetal cell is an erythroblast.
- 88. The method of claim 41, wherein the fetal cell is a trophoblast.
- 89. The method of claim 41, wherein determining whether the abnormality exists in said fetal cell comprises the steps of:
(d) contacting the maternal blood sample with a diagnostic probe under conditions that allow hybridization of the diagnostic probe to a diagnostic target sequence in the fetal cell, wherein the manner of hybridization of the diagnostic probe to the diagnostic target sequence is indicative of whether the abnormality exists in the fetal cell; and (e) determining the manner in which the diagnostic probe hybridizes to the target sequence, thereby determining whether the abnormality exists in the fetal cell.
- 90. The method of claim 89, wherein steps (a) and (d) are performed simultaneously.
- 91. The method of claim 90, further comprising, prior to steps (a) and (d), contacting the maternal blood sample with a first fixative, wherein the first fixative comprises 4% formalin and has a pH of 6-8.
- 92. The method of claim 91, further comprising, following steps (a) and (d), contacting the maternal blood sample with a second fixative following, wherein the second fixative comprises 4% formalin and has a pH of less than 6.
- 93. A method for identifying a nucleic acid useful as a probe for fetal cells in the maternal circulation, comprising the steps of:
(a) performing differential expression analysis on RNA or cDNA obtained from fetal liver myeloid cells of less than 22 weeks of gestation relative to RNA or cDNA obtained from more mature liver or non-liver myeloid cells; and (b) identifying an RNA or cDNA species that is selectively or specifically expressed in the fetal liver myeloid cells, wherein the RNA or cDNA species that is selectively or specifically expressed in the fetal liver myeloid cells is useful as a probe for fetal cells in the maternal circulation.
- 94. The method of claim 93, wherein the fetal liver is human fetal liver.
- 95. The method of claim 93, wherein the fetal liver myeloid cells are obtained before 20 weeks of gestation.
- 96. The method of claim 95, wherein the fetal liver myeloid cells are obtained between 10 and 15 weeks of gestation.
- 97. The method of claim 95, wherein the more mature myeloid cells are fetal cord blood cells obtained after 22 weeks of gestation, fetal peripheral blood cells obtained after 22 weeks of gestation, or fetal liver myeloid cells obtained after about 22 weeks of gestation.
- 98. The method of claim 93, wherein the mature myeloid cells are adult bone marrow cells or adult peripheral blood cells.
- 99. The method of claim 93, wherein the differential expression analysis comprises subtraction suppression hybridization (SSH).
- 100. A kit comprising in one or more containers
(a) a first probe, said first probe comprising:
(i) a nucleotide sequence corresponding to SEQ ID NO:10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42; (ii) a nucleotide sequence having at least 90% sequence identity to at least 20 consecutive nucleotides of SEQ ID NO: 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42; or (iii) a nucleotide sequence having at least 80% sequence identity to at least 40 consecutive nucleotides of SEQ ID NO: 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42, which first probe selectively or specifically hybridizes to mRNA in fetal cells if present in a maternal blood sample; and (b) instructions for diagnostic use or a label indicating regulatory approval for diagnostic use.
- 101. The kit of claim 108, further comprising an antibody that selectively or specifically binds to fetal cells in a maternal blood sample.
- 102. The kit of claim 108, further comprising a second probe that selectively or specifically hybridizes to mRNA in fetal cells if present in a maternal blood sample.
- 103. The kit of claim 102, wherein the second probe comprises:
(a) a nucleotide sequence corresponding to SEQ ID NO:10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42; (b) a nucleotide sequence having at least 90% sequence identity to at least 20 consecutive nucleotides of SEQ ID NO:10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42; or (c) a nucleotide sequence having at least 80% sequence identity to 40 consecutive nucleotides of SEQ ID NO:10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42.
- 104. The kit of claim 102, wherein the first probe and the second probe correspond to the same mRNA.
- 105. The kit of claim 102, wherein the first probe and the second probe correspond to different mRNAs.
- 106. The kit of claim 102, wherein the first probe and the second probe are labeled with the same type of label.
- 107. A method for detecting a fetal cell in a maternal blood sample, comprising the steps of:
(a) performing differential expression analysis on RNA or cDNA obtained from fetal liver myeloid cells relative to RNA or cDNA obtained from mature myeloid cells; (b) identifying an RNA or cDNA species that is selectively or specifically expressed in the fetal liver myeloid cells, thereby identifying an RNA or cDNA species that is useful as a probe for fetal cells in the maternal circulation; (c) contacting the maternal blood sample with a probe comprising a nucleotide sequence corresponding to all or a portion of the RNA or cDNA of step (b); and (d) identifying whether or not said maternal blood sample comprises a cell that comprises mRNA that detectably hybridizes to the first probe, thereby detecting whether or not said maternal blood sample contains a fetal cell.
- 108. A method for diagnosing an abnormality in a fetal cell, comprising the steps of:
(a) performing differential expression analysis on RNA or cDNA obtained from fetal liver myeloid cells relative to RNA or cDNA obtained from mature myeloid cells; (b) identifying an RNA or cDNA species that is selectively or specifically expressed in the fetal liver myeloid cells, thereby identifying an RNA or cDNA species that is useful as a probe for fetal cells in the maternal circulation; (c) contacting the maternal blood sample with a probe comprising a nucleotide sequence corresponding to all or a portion of the RNA or cDNA of step (b); (d) identifying whether or not said maternal blood sample comprises a cell that comprises mRNA that detectably hybridizes to the first probe, thereby detecting whether or not said maternal blood sample contains a fetal cell; and (e) if the maternal blood sample contains a fetal cell, determining whether the abnormality exists in said fetal cell, thereby diagnosing the abnormality.
- 109. An isolated nucleic acid molecule selected from the group consisting of
(a) a nucleic acid molecule having a nucleotide sequence which is at least 90% identical to the nucleotide sequence of any of SEQ ID NOs:10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42, or a complement thereof; (b) a nucleic acid molecule comprising at least 15 nucleotide residues and having a nucleotide sequence identical to at least 15 consecutive nucleotide residues of any of SEQ ID NOs:10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42, or a complement thereof, (c) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of any of SEQ ID NOs:43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, or 78; (d) a nucleic acid molecule which encodes a fragment at least 10 consecutive amino acid residues of a polypeptide comprising the amino acid sequence of any of SEQ ID NOs:43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, or 78; (e) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of any SEQ ID NOs:43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, or 78; wherein the fragment comprises consecutive amino acid residues corresponding to at least half of the full length of any of said SEQ ID NOs; and (f) a nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of any of SEQ ID NOs:43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, or 78, wherein the nucleic acid molecule hybridizes with a nucleic acid molecule consisting of the nucleotide sequence of any of SEQ ID NOs:10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42 under stringent conditions, or a complement thereof.
- 110. The isolated nucleic acid molecule of claim 109, which is selected from the group consisting of:
(a) a nucleic acid having the nucleotide sequence of any of SEQ ID NOs:10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42, or a complement thereof; and (b) a nucleic acid molecule which encodes a polypeptide having the amino acid sequence of any of SEQ ID NOs:43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, or 78, or a complement thereof.
- 111. The nucleic acid molecule of claim 109, further comprising a vector nucleic acid sequence.
- 112. The nucleic acid molecule of claim 109, further comprising a nucleic acid sequence encoding a heterologous polypeptide.
- 113. A host cell which contains the nucleic acid molecule of claim 109.
- 114. The host cell of claim 113 which is a mammalian host cell.
- 115. A non-human mammalian host cell containing the nucleic acid molecule of claim 109.
- 116. An isolated polypeptide selected from the group consisting of:
(a) a fragment of a polypeptide comprising the amino acid sequence of any of SEQ ID NOs:43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, or 78; (b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of any of SEQ ID NOs:43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, or 78, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes with a nucleic acid molecule consisting of the nucleotide sequence of any of SEQ ID NOs:10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42 under stringent conditions, or a complement thereof; and (c) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 90% identical to a nucleic acid consisting of the nucleotide sequence of any of SEQ ID NOs:10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42, or a complement thereof.
- 117. The isolated polypeptide of claim 116 having the amino acid sequence of any of SEQ ID NOs:43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, or 78.
- 118. The polypeptide of claim 116, wherein the amino acid sequence of the polypeptide further comprises heterologous amino acid residues.
- 119. An antibody which selectively binds with the polypeptide of claim 116.
- 120. A method for producing a polypeptide selected from the group consisting of:
(a) a polypeptide comprising the amino acid sequence of any of SEQ ID NOs: 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, or 78; (b) a polypeptide comprising a fragment of at least 10 contiguous amino acids of the amino acid sequence of any of SEQ ID NOs:43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, or 78; and (c) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of any of SEQ ID NOs:43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, or 78, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes with a nucleic acid molecule consisting of the nucleotide sequence of any of SEQ ID NOs:10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41 or 42, or a complement thereof under stringent conditions; the method comprising culturing the host cell of claim 113 under conditions in which the nucleic acid molecule is expressed.
Parent Case Info
[0001] The present application claims priority of U.S. provisional application No. 60/248,882 under 35 U.S.C. §119(e), which application is incorporated by reference herein in its entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60248882 |
Nov 2000 |
US |