Compilations of nucleic acids and arrays and methods of using them

1. An array comprising: a plurality of nucleic acid segments, wherein each nucleic acid segment is immobilized to a discrete and known spot on a substrate surface to form an array of nucleic acids, and each spot comprises a segment of genomic nucleic acid selected to detect a genetic syndrome, wherein the array-immobilized genomic nucleic acid segments are covalently bound to the substrate surface through a compound having the general formula: R 1 —X—R 2 , and wherein R 1 is a cyclic ether, an aldehyde, or a chloromethylphenyl moiety; X is a moiety chemically suitable for linking the R 1 moiety to the R 2 moiety, and the R 2 moiety has the general formula

wherein R 3 , R 4 and R 5 comprise identical or different alkoxy groups or chloro groups.

2. The away of claim 1 , further comprising at least one spot comprising a nucleic acid segment acting as a positive control.

3. The array of claim 1 , further comprising at least one spot comprising a nucleic acid segment acting as a negative control.

4. The array of claim 1 , wherein the array-immobilized genomic nucleic acid segments in a first spot are non-overlapping in sequence compared to the array-immobilized genomic nucleic acid segments in a second spot.

5. The array of claim 4 , wherein the array-immobilized genomic nucleic acid segments in the first spot are non-overlapping in sequence compared to the array-immobilized genomic nucleic acid segments in all other genomic nucleic acid-comprising spots on the array.

6. The array of claim 1 , wherein at least one genomic nucleic acid segment is spotted in duplicate or triplicate on the array.

7. The array of claim 1 , wherein the duplicate spot or triplicate spot has a different amount of nucleic acid segments immobilized.

8. The array of claim 6 , wherein all the genomic nucleic acid segments are spotted in duplicate or triplicate on the array.

9. The array of claim 1 , wherein about 95% of the array-immobilized genomic nucleic acid segments comprise a label.

10. The array of claim 1 , wherein about 98% of the array-immobilized genomic nucleic acid segments comprise a label.

11. The array of claim 1 , wherein 100% of the array-immobilized genomic nucleic acid segments comprise a label.

12. The array of claim 1 , wherein at least one nucleic acid segment is cloned in a construct comprising an artificial chromosome.

13. The array of claim 12 , wherein the artificial chromosome comprises a bacterial artificial chromosome (BAC).

14. The array of claim 12 , wherein the artificial chromosome is selected from the group consisting of a human artificial chromosome (HAC) a yeast artificial chromosome (YAC), a transformation-competent artificial chromosome (TAC) and a bacteriophage P1-derived artificial chromosome (PAC).

15. The array of claim 1 , wherein at least one nucleic acid segment is cloned in a construct comprising a vector selected from the group consisting of a cosmid vector, a plasmid vector and a viral vector.

16. The array of claim 1 , wherein at least one of the nucleic acid segments is between about 50 kilobases to about 500 kilobases in length.

17. The array of claim 16 , wherein the at least one nucleic acid segment is between about 100 kilobases to about 400 kilobases in length.

18. The array of claim 17 , wherein the at least one nucleic acid segment is about 300 kilobases in length.

19. A compilation of nucleic acids for diagnosis of a genetic syndrome, the compilation comprising a plurality of nucleic acid segments, wherein each nucleic acid segment comprises a segment of genomic nucleic acid selected to detect a genetic syndrome, wherein the nucleic acid segments further comprise a compound having the general formula

R 1 —X—Si(OR 2 ) m (Cl) n (R) k ,

wherein m+k is the integer 3, and n can be 0 if m is greater than 0, or n+k is the integer 3 and m can be 0 if n is greater than 0; X is an inert linker; R 1 comprises a group reactive toward the biological molecule; R is an alkyl group; and R 2 is an alkyl group.

20. The compilation of nucleic acids of claim 19 , wherein the nucleic acid segments further comprise a cloning vehicle.

21. The compilation of nucleic acids of claim 19 , wherein the nucleic acid segments are immobilized onto a surface.

22. The compilation of nucleic acids of claim 21 , wherein the nucleic acid segments are immobilized on a surface as an array.

23. The compilation of nucleic acids of claim 19 , wherein about 95% of the nucleic acid segments comprise a label.

24. The compilation of nucleic acids of claim 19 , wherein about 98% of the nucleic acid segments comprise a label.

25. The compilation of nucleic acids of claim 19 , wherein 100% of the nucleic acid segments comprise a label.

26. The compilation of nucleic acids of claim 19 , wherein at least one nucleic acid segment is cloned in a construct comprising an artificial chromosome.

27. The compilation of nucleic acids of claim 26 , wherein the artificial chromosome comprises a bacterial artificial chromosome (BAC).

28. The compilation of nucleic acids of claim 26 , wherein the artificial chromosome is selected from the group consisting of a human artificial chromosome (HAC), a yeast artificial chromosome (YAC), a transformation-competent artificial chromosome (TAC) and a bacteriophage P1-derived artificial chromosome (PAC).

29. The compilation of nucleic acids of claim 19 , wherein at least one nucleic acid segment is cloned in a construct comprising a vector selected from the group consisting of a cosmid vector, a plasmid vector and a viral vector.

30. The compilation of nucleic acids of claim 19 , wherein the nucleic acid segments are between about 50 kilobases to about 500 kilobases in length.

31. The compilation of nucleic acids of claim 30 , wherein the nucleic acid segments are between about 100 kilobases to about 400 kilobases in length.

32. The compilation of nucleic acids of claim 31 , wherein the cloned nucleic acid segments are between about 150 kilobases and about 300 kilobases in length.

33. An array comprising: a plurality of nucleic acid segments, wherein each nucleic acid segment is immobilized to a discrete and known spot on a substrate surface to form an array of nucleic acids, and each spot comprises a segment of genomic nucleic acid selected to detect a genetic syndrome, wherein the array-immobilized genomic nucleic acid segments are covalently bound to the substrate surface through a compound having the general formula: R 1 —X—R 2 , wherein R 1 is an amino group, R 2 is an alkoxysilane group or a chlorohalide group; and X is a moiety chemically suitable for linking the R 1 group and the R 2 group.

34. The array of claim 31 , further comprising at least one spot comprising a nucleic acid segment acting as a positive control.

35. The array of claim 31 , further comprising at least one spot comprising a nucleic acid segment acting as a negative control.

36. The array of claim 31 , wherein the array-immobilized genomic nucleic acid segments in a first spot are non-overlapping in sequence compared to the array-immobilized genomic nucleic acid segments in a second spot.

37. The array of claim 36 , wherein the array-immobilized genomic nucleic acid segments in the first spot are non-overlapping in sequence compared to the array-immobilized genomic nucleic acid segments in all other genomic nucleic acid-comprising spots on the array.

38. The array of claim 31 , wherein at least one genomic nucleic acid segment is spotted in duplicate or triplicate on the array.

39. The array of claim 38 , wherein the duplicate spot or triplicate spot has a different amount of nucleic acid segments immobilized.

40. The array of claim 38 , wherein all the genomic nucleic acid segments are spotted in duplicate or triplicate on the array.

41. The array of claim 31 , wherein about 95% of the array-immobilized genomic nucleic acid segments comprise a label.

42. The array of claim 31 , wherein about 98% of the array-immobilized genomic nucleic acid segments comprise a label.

43. The array of claim 31 , wherein 100% of the array-immobilized genomic nucleic acid segments comprise a label.

44. The array of claim 31 , wherein at least one nucleic acid segment is cloned in a construct comprising an artificial chromosome.

45. The array of claim 44 , wherein the artificial chromosome comprises a bacterial artificial chromosome (BAC).

46. The array of claim 44 , wherein the artificial chromosome is selected from the group consisting of a human artificial chromosome (HAC) a yeast artificial chromosome (YAC), a transformation-competent artificial chromosome (TAC) and a bacteriophage P1-derived artificial chromosome (PAC).

47. The array of claim 31 , wherein at least one nucleic acid segment is cloned in a construct comprising a vector selected from the group consisting of a cosmid vector, a plasmid vector and a viral vector.

48. The array of claim 31 , wherein at least one of the nucleic acid segments is between about 50 kilobases to about 500 kilobases in length.

49. The array of claim 48 , wherein the at least one nucleic acid segment is between about 100 kilobases to about 400 kilobases in length.

50. The array of claim 49 , wherein the at least one nucleic acid segment is about 300 kilobases in length.

51. A method for selecting a genomic nucleic acid segment for use as a hybridization target in a comparative genomic hybridization (CGH) reaction for the detection of a chromosomal aneuploidy comprising (a) selecting a chromosomal segment that hybridizes to a single locus comprising a segment of the chromosome comprising the aneuploidy to be detected; (b) selecting a chromosomal segment having at least 15% to 25% unique sequence such that at least 75% to 85% of the sequence within the chromosomal segment is repetitive, except for chromosomal segments from the X chromosome or Y chromosome, which can have up to 90% to 95% repetitive sequences; and (c) selecting a segment selected in both step (a) and step (b), thereby selecting a genomic nucleic acid segment for use as a hybridization target in a comparative genomic hybridization (CGH) reaction for the detection of a chromosomal aneuploidy.

52. The method of claim 51 comprising selecting a chromosomal segment having at least 15% unique sequence.

53. A compilation of nucleic acids for diagnosis of a genetic syndrome, the compilation comprising a plurality of nucleic acid segments, wherein each nucleic acid segment comprises a segment of genomic nucleic acid selected to detect a genetic syndrome, wherein the nucleic acid segments further comprise a compound having the general formula: R 1 —X—R 2 , wherein R 1 is a cyclic ether, an aldehyde, or a chloromethylphenyl moiety; X is a moiety chemically suitable for linking the R 1 moiety to the R 2 moiety, and the R 2 moiety has the general formula

wherein R 3 , R 4 and R 5 comprise identical or different alkoxy groups or chloro groups.

54. The compilation of nucleic acids of claim 53 , wherein the nucleic acid segments further comprise a cloning vehicle.

55. The compilation of nucleic acids of claim 53 , wherein the nucleic acid segments are immobilized onto a surface.

56. The compilation of nucleic acids of claim 55 , wherein the nucleic acid segments are immobilized on a surface as an array.

57. The compilation of nucleic acids of claim 53 , wherein about 95% of the nucleic acid segments comprise a label.

58. The compilation of nucleic acids of claim 53 , wherein about 98% of the nucleic acid segments comprise a label.

59. The compilation of nucleic acids of claim 53 , wherein 100% of the nucleic acid segments comprise a label.

60. The compilation of nucleic acids of claim 53 , wherein at least one nucleic acid segment is cloned in a construct comprising an artificial chromosome.

61. The compilation of nucleic acids of claim 60 , wherein the artificial chromosome comprises a bacterial artificial chromosome (BAC).

62. The compilation of nucleic acids of claim 60 , wherein the artificial chromosome is selected from the group consisting of a human artificial chromosome (HAC), a yeast artificial chromosome (YAC), a transformation-competent artificial chromosome (TAC) and a bacteriophage P1-derived artificial chromosome (PAC).

63. The compilation of nucleic acids of claim 53 , wherein at least one nucleic acid segment is cloned in a construct comprising a vector selected from the group consisting of a cosmid vector, a plasmid vector and a viral vector.

64. The compilation of nucleic acids of claim 53 , wherein the nucleic acid segments are between about 50 kilobases to about 500 kilobases in length.

65. The compilation of nucleic acids of claim 64 , wherein the nucleic acid segments are between about 100 kilobases to about 400 kilobases in length.

66. The compilation of nucleic acids of claim 65 , wherein the cloned nucleic acid segments are between about 150 kilobases and about 300 kilobases in length.

67. A compilation of nucleic acids for diagnosis of a genetic syndrome, the compilation comprising a plurality of nucleic acid segments, wherein each nucleic acid segment comprises a segment of genomic nucleic acid selected to detect a genetic syndrome, wherein the nucleic acid segments further comprise a compound having the general formula: R 1 —X—R 2 , wherein R 1 is an amino group, R 2 is an alkoxysilane group or a chlorohalide group; and X is a moiety chemically suitable for linking the R 1 group and the R 2 group.

68. The compilation of nucleic acids of claim 67 , wherein the nucleic acid segments further comprise a cloning vehicle.

69. The compilation of nucleic acids of claim 67 , wherein the nucleic acid segments are immobilized onto a surface.

70. The compilation of nucleic acids of claim 69 , wherein the nucleic acid segments are immobilized on a surface as an array.

71. The compilation of nucleic acids of claim 67 , wherein about 95% of the nucleic acid segments comprise a label.

72. The compilation of nucleic acids of claim 67 , wherein about 98% of the nucleic acid segments comprise a label.

73. The compilation of nucleic acids of claim 67 , wherein 100% of the nucleic acid segments comprise a label.

74. The compilation of nucleic acids of claim 67 , wherein at least one nucleic acid segment is cloned in a construct comprising an artificial chromosome.

75. The compilation of nucleic acids of claim 74 , wherein the artificial chromosome comprises a bacterial artificial chromosome (BAC).

76. The compilation of nucleic acids of claim 74 , wherein the artificial chromosome is selected from the group consisting of a human artificial chromosome (HAC), a yeast artificial chromosome (YAC), a transformation-competent artificial chromosome (TAC) and a bacteriophage P1-derived artificial chromosome (PAC).

77. The compilation of nucleic acids of claim 67 , wherein at least one nucleic acid segment is cloned in a construct comprising a vector selected from the group consisting of a cosmid vector, a plasmid vector and a viral vector.

78. The compilation of nucleic acids of claim 67 , wherein the nucleic acid segments are between about 50 kilobases to about 500 kilobases in length.

79. The compilation of nucleic acids of claim 78 , wherein the nucleic acid segments are between about 100 kilobases to about 400 kilobases in length.

80. The compilation of nucleic acids of claim 79 , wherein the cloned nucleic acid segments are between about 150 kilobases and about 300 kilobases in length.

81. An array comprising: a plurality of nucleic acid segments, wherein each nucleic acid segment is immobilized to a discrete and known spot on a substrate surface to form an array of nucleic acids, and each spot comprises a segment of genomic nucleic acid selected to detect a genetic syndrome, wherein the array-immobilized genomic nucleic acid segments are covalently bound to the substrate surface through a compound having the general formula

R 1 —X—Si(OR 2 ) m (Cl) n (R) k ,

wherein m+k is the integer 3, and n can be 0 if m is greater than 0, or n+k is the integer 3 and m can be 0 if n is greater than 0; X is an inert linker; R 1 comprises a group reactive toward a biological molecule; R is an alkyl group; and, R 2 is an alkyl group.

82. The array of claim 81 , further comprising at least one spot comprising a nucleic acid segment acting as a positive control.

83. The array of claim 81 , further comprising at least one spot comprising a nucleic acid segment acting as a negative control.

84. The array of claim 81 , wherein the array-immobilized genomic nucleic acid segments in a first spot are non-overlapping in sequence compared to the array-immobilized genomic nucleic acid segments in a second spot.

85. The array of claim 84 , wherein the array-immobilized genomic nucleic acid segments in the first spot are non-overlapping in sequence compared to the array-immobilized genomic nucleic acid segments in all other genomic nucleic acid-comprising spots on the array.

86. The array of claim 81 , wherein at least one genomic nucleic acid segment is spotted in duplicate or triplicate on the array.

87. The array of claim 86 , wherein the duplicate spot or triplicate spot has a different amount of nucleic acid segments immobilized.

88. The array of claim 86 , wherein all the genomic nucleic acid segments are spotted in duplicate or triplicate on the array.

89. The array of claim 81 , wherein about 95% of the array-immobilized genomic nucleic acid segments comprise a label.

90. The array of claim 81 , wherein about 98% of the array-immobilized genomic nucleic acid segments comprise a label.

91. The array of claim 81 , wherein 100% of the array-immobilized genomic nucleic acid segments comprise a label.

92. The array of claim 81 , wherein at least one nucleic acid segment is cloned in a construct comprising an artificial chromosome.

93. The array of claim 92 , wherein the artificial chromosome comprises a bacterial artificial chromosome (BAC).

94. The array of claim 92 , wherein the artificial chromosome is selected from the group consisting of a human artificial chromosome (HAC) a yeast artificial chromosome (YAC), a transformation-competent artificial chromosome (TAC) and a bacteriophage P1-derived artificial chromosome (PAC).

95. The array of claim 81 , wherein at least one nucleic acid segment is cloned in a construct comprising a vector selected from the group consisting of a cosmid vector, a plasmid vector and a viral vector.

96. The array of claim 81 , wherein at least one of the nucleic acid segments is between about 50 kilobases to about 500 kilobases in length.

97. The array of claim 96 , wherein the at least one nucleic acid segment is between about 100 kilobases to about 400 kilobases in length.

98. The array of claim 97 , wherein the at least one nucleic acid segment is about 300 kilobases in length.