WO1995011995B1 - Arrays of nucleic acid probes on biological chips - Google Patents

Arrays of nucleic acid probes on biological chips

Info

Publication number
WO1995011995B1
WO1995011995B1 PCT/US1994/012305 US9412305W WO9511995B1 WO 1995011995 B1 WO1995011995 B1 WO 1995011995B1 US 9412305 W US9412305 W US 9412305W WO 9511995 B1 WO9511995 B1 WO 9511995B1
Authority
WO
WIPO (PCT)
Prior art keywords
array
probe
reference sequence
probes
sequence
Prior art date
Application number
PCT/US1994/012305
Other languages
French (fr)
Other versions
WO1995011995A1 (en
Filing date
Publication date
Application filed filed Critical
Priority to EP95900441A priority Critical patent/EP0730663B1/en
Priority to JP7512811A priority patent/JPH09507121A/en
Priority to AU81266/94A priority patent/AU8126694A/en
Priority to DE69433180T priority patent/DE69433180T2/en
Publication of WO1995011995A1 publication Critical patent/WO1995011995A1/en
Publication of WO1995011995B1 publication Critical patent/WO1995011995B1/en
Priority to US08/510,521 priority patent/US7115364B1/en
Priority to US08/630,427 priority patent/US6156501A/en
Priority to US08/648,709 priority patent/US6045996A/en
Priority to US08/778,794 priority patent/US6309823B1/en
Priority to US09/393,389 priority patent/US6632605B1/en
Priority to US09/510,378 priority patent/US7399584B2/en
Priority to US09/798,260 priority patent/US20030165830A1/en
Priority to US10/113,885 priority patent/US20030134291A1/en
Priority to US10/229,319 priority patent/US20030054393A1/en
Priority to US10/402,333 priority patent/US20030232361A1/en
Priority to US10/418,414 priority patent/US7375198B2/en
Priority to US11/367,800 priority patent/US20060229824A1/en
Priority to US11/388,199 priority patent/US20060263807A1/en
Priority to US11/401,482 priority patent/US7846659B2/en
Priority to US11/506,176 priority patent/US20120329677A9/en
Priority to US12/124,061 priority patent/US7794943B2/en
Priority to US12/878,743 priority patent/US20110092382A1/en
Priority to US12/959,359 priority patent/US20130150248A1/en

Links

Abstract

The invention provides chips of immobilized probes, and methods employing the chips, for comparing a reference polynucleotide sequence of known sequence with a target sequence showing substantial similarity with the reference sequence, but differing in the presence of e.g., mutations.

Claims

AMENDED CLAIMS
[received by the International Bureau on 19 April 1995 (19.04.95); original claims 1,2,65,79-108 amended; new claim 109 added other claims unchanged (9 pages)]
1. An array of oligonucleotide probes immobilized on a solid support, the array comprising at least two sets of oligonucleotide probes, (1) a first probe set comprising a plurality of probes, each probe comprising a segment of at least three nucleotides exactly complementary to a subsequence of a reference sequence, the segment including at least one interrogation position complementary to a corresponding nucleotide in the reference sequence, (2) a second probe set comprising a corresponding probe for each probe in the first probe set, the corresponding probe in the second probe set being identical to a sequence comprising the corresponding probe from the first probe set or a subsequence of at least three nucleotides thereof that includes the at least one interrogation position, except that the at least one interrogation position is occupied by a different nucleotide in each of the two corresponding probes from the first and second probe sets; wherein the probes in the first probe set have at least two interrogation positions respectively corresponding to each of two contiguous nucleotides in the reference sequence.
2. An array of oligonucleotide probes immobilized on a solid support, the array comprising at least four sets of oligonucleotide probes, (1) a first probe set comprising a plurality of probes, each probe comprising a segment of at least three nucleotides exactly complementary to a subsequence of a reference sequence, the segment including at least one interrogation position complementary to a corresponding nucleotide in the reference sequence, (2) second, third and fourth probe sets, each comprising a corresponding probe for each probe in the first probe set, the probes in the second, third and fourth probe sets being identical to a sequence comprising the corresponding probe from the first probe set or a subsequence (d) determining which probes, relative to one another, in the array bind specifically to the target sequence; wherein the relative specific binding of the probes to the reference and the target sequence indicates whether the reference sequence is the same or different from the target sequence.
64. The method of claim 63, wherein the reference sequence has a first label and the second reference sequence has a second label different from the first label, and steps (a) and (c) are performed simultaneously.
HIV Chip 65. The array of claim 1 or 2, wherein the reference sequence is from a human immunodeficiency virus.
66. The array of claim 65, wherein the reference sequence is from a reverse transcriptase gene of the human immunodeficiency virus.
67. The array of claim 66, wherein the reference sequence is from a protease gene of the human immunodeficiency virus.
68. The array of claim 66, wherein the reference sequence is a full-length reverse transcriptase gene.
69. The array of claim 68 comprising at least 3200 oligonucleotide probes.
70. The array of claim 66, wherein the HIV gene is from the BRU HIV strain.
71. The array of claim 66, wherein the HIV gene is from the SF2 HIV strain. 72. The array of claim 28, wherein the reference sequence is from the coding strand of a reverse transcriptase gene of a human immunodeficiency virus and the second reference sequence is from the noncoding strand of the reverse transcriptase gene.
73. The array of claim 28, wherein the first reference sequence is from a reverse transcriptase gene of a human immunodeficiency virus and the second reference sequence comprises a subsequence of the first reference sequence with a substitution of at least one nucleotide.
74. The array of claim 73, wherein the substitution confers drug resistance to a human immunodeficiency virus comprising the second reference sequence.
75. The array of claim 28, wherein the first and second reference sequences are from a reverse transcriptase gene from first and second strains of a human immunodeficiency virus.
76. The array of claim 28, wherein the first reference sequence is from a reverse transcriptase gene of a human immunodeficiency virus and the second reference sequence is from a 16S RNA, or DNA encoding the 16S RNA, from a pathogenic microorganism.
77. The array of claim 28, wherein the first reference sequence is from a reverse transcriptase gene of a human immunodeficiency virus and the second reference sequence is from a protease gene of the human immunodeficiency virus.
78. The method of claim 54, wherein the reference sequence is from a human immunodeficiency virus.
79. The method of claim 78, further comprising the step of altering a drug treatment program based on the relative specific binding of the probes. 80. The method of claim 78, wherein the target sequence is from a second human immunodeficiency virus.
81. The method of claim 80, wherein the target sequence has a substituted nucleotide relative to the reference sequence in at least one undetermined position, and the relative specific binding of the probes indicates the location of the position and the nucleotide occupying the position in the target sequence.
82. The method of claim 81, wherein the target sequence has a substituted nucleotide relative to the reference sequence in at least one position, the substitution conferring drug resistance to the human immunodeficiency virus, and the relative specific binding of the probes reveals the substitution.
83. The method of claim 78, wherein: the hybridizing step comprises hybridizing the target nucleic acid and a second target nucleic acid, the second target sequence being from a reverse transcriptase gene of a third human immunodeficiency virus, to the array; and the determining step comprises determining which probes, relative to one another, in the array bind specifically to the target nucleic acid or the second target nucleic acid, the relative specific binding of the probes indicating whether the target sequence is the same or different from the reference sequence and whether the second target sequence is the same or different from the reference sequence.
84. The method of claim 83, wherein the first target sequence has a first label and the second target sequence has a second label different from the first label.
85. The method of claim 83, wherein undetermined first and second proportions of the first and second target sequences are hybridized to the array and the specific binding indicates the proportions.
86. A method of treating a patient infected with an HIV virus, the method comprising: (a) hybridizing a tissue sample from the patient containing a target nucleic acid to an array of oligonucleotide probes immobilized on a solid support, the array comprising: (1) a first probe set comprising a plurality of probes, each probe comprising a segment of at least three nucleotides exactly complementary to a subsequence of a reference sequence comprising an HIV gene, the segment including at least one interrogation position complementary to a corresponding nucleotide in the reference sequence, (2) a second probe set comprising a corresponding probe for each probe in the first probe set, the corresponding probe in the second probe set being identical to a sequence comprising the corresponding probe from the first probe set or a subsequence of at least three nucleotides thereof that includes the at least one interrogation position, except that the at least one interrogation position is occupied by a different nucleotide in each of the two corresponding probes from the first and second probe sets; wherein the probes in the first probe set have at least three interrogation positions respectively corresponding to each of at least three nucleotides in the reference sequence, and (b) determining which probes, relative to one another, in the array bind specifically to the target nucleic acid, the relative specific binding of the probes identifying a mutation in the target sequence relative to the reference sequence; and (c) administering to the patient a drug effective against an HIV virus bearing the mutation. CFTR Chip 87. The array of claim 1 or 2, wherein the reference sequence is from a CFTR gene.
88. The array of claim 87, wherein the reference sequence is exon 10 of a CFTR gene, and said array comprises over 1000 oligonucleotide probes, 10 to 18 nucleotides in length.
89. The array of claim 87, wherein said array comprises a set of probes comprising a specific nucleotide sequence selected from the group of sequences comprising: 3'-TTTATAXTAG; 3'- TTATAGXAGA; 3«- TATAGTXGAA; 3'- ATAGTAXAAA; 3'- TAGTAGXAAC; 3'- AGTAGAXACC; 3'- GTAGAAXCCA; 3'- TAGAAAXCAC; and 3'- AGAAACXACA; wherein each set comprises 4 probes, and X is individually A, G, C, and T for each set.
90. The array of claim 87, wherein said group of sequences comprises: 3•-TTTATAXTAGAAACC; 3'- TTATAGXAGAAACCA; 3'- TATAGTXGAAACCAC; 3'- ATAGTAXAAACCACA; 3«- TAGTAGXAACCACAA; 3'- AGTAGAXACCACAAA; 3'- GTAGAAXCCACAAAG; 3'- TAGAAAXCACAAAGG; and 3'- AGAAACXACAAAGGA; wherein each set comprises 4 probes, and X is individually A, G, C, and T for each set.
91. The array of claim 32, wherein the forty first reference sequences are from a CFTR gene. 5
92. The array of claim 91, wherein each of the forty first reference sequences includes a site of a mutation and at least one adjacent nucleotide.
93. The array of claim 92, wherein each of the forty first reference sequences comprises at least five contiguous nucleotides from a CFTR gene.
94. The array of claim 91, wherein at least one first reference sequence is a from the coding strand of the cystic fibrosis gene and at least one first reference sequence is from the noncoding strand of the CFTR gene.
95. An array of oligonucleotide probes immobilized on a solid support, the array comprising at least a group of probes comprising: a wildtype probe exactly complementary to a subsequence of a reference sequence from a CFTR gene, the segment having at least five interrogation positions corresponding to five contiguous nucleotides in the reference sequence, a first set of three mutant probes, each identical to the wildtype probe, except in a first of the five interrogation positions, which is occupied by a different nucleotide in each of the three mutant probes and the wildtype probe; a second set of three mutant probes, each identical to the wildtype probe, except in a second of the five interrogation positions, which is occupied by a different nucleotide in each of the three mutant probes and the wildtype probe; a third set of three mutant probes, each identical to the wildtype probe, except in a third of the five interrogation positions, which is occupied by a different nucleotide in each of the three mutant probes and the wildtype probe; a fourth set of three mutant probes, each identical to the wildtype probe, except in a fourth of the five interrogation positions, which is occupied by a different nucleotide in each of the three mutant probes and the wildtype probe; a fifth set of three mutant probes, each identical to the wildtype probe, except in a fifth of the five interrogation positions, which is occupied by a different nucleotide in each of the three mutant probes and the wildtype probe.
96. The array of claim 95 comprising first and second groups of probes, each group as defined by claim 93, the first group comprising a wildtype probe exactly complementary to a first reference sequence, and the second group comprising a wildtype probe exactly complementary to a second reference sequence, wherein the second reference sequence is a mutated form of the first reference sequence.
97. The method of claim 56, wherein the target sequence and the second target sequence are from heterozygous alleles of a CFTR gene.
F53 Chip 98. The array of claim 1 or 2, wherein the reference sequence is a sequence from a p53 gene.
99. The array of claim 2, wherein the reference sequence is from an h-MLHl gene.
100. The array of claim 2, wherein the reference sequence is from an MSH2 gene.
101. The array of claim 28, wherein the reference sequence is from a human P53 gene and the second reference sequence is from an hMLHl gene.
102. The array of claim 101, further comprising: ninth, tenth, eleventh and twelfth probe sets, (1) the ninth probe set comprising a plurality of probes, each probe comprising a segment of at least three nucleotides exactly complementary to a subsequence of a third reference sequence, the segment including at least one 6
interrogation position complementary to a corresponding nucleotide in the third reference sequence, (2) the tenth, eleventh and twelfth probe sets, each comprising a corresponding probe for each probe in the ninth probe set, the probes in the tenth, eleventh and twelfth probe sets being identical to a sequence comprising the corresponding probe from the ninth probe set or a subsequence of at least three nucleotides thereof that includes the at least one interrogation position, except that the at least one interrogation position is occupied by a different nucleotide in each of the four corresponding probes from the ninth, tenth, eleventh and twelfth probe sets.
103. The array of claim 98, wherein the first probe set has at least 60 interrogation positions corresponding to at 60 contiguous nucleotides from exon 6.
104. The array of claim 99, wherein the reference sequence is exon 5 of a p53 gene, the probes are 17 nucleotides long, and the first set of probes is exactly complementary to the reference sequence, and the at least one interrogation position is at position 7, relative to a 3'-end of each probe, which 3'-end is covalently attached to the substrate. Mitochondrial Chip 105. The array of claim 1 or 2, wherein the reference sequence is from a mitochondrial genome.
106. The array of claim 105, wherein said reference sequence is a sequence of a D-loop region. 107. The array of claim 106, wherein D-loop region is full-length. 108. The array of claim 105, wherein said reference sequence is at least 90% of a full-length mitochondrial genome. 109. The array of claim 105, wherein the reference sequence is bounded by positions 16280 to 356 of the mitochondrial genome.
PCT/US1994/012305 1993-06-25 1994-10-26 Arrays of nucleic acid probes on biological chips WO1995011995A1 (en)

Priority Applications (22)

Application Number Priority Date Filing Date Title
EP95900441A EP0730663B1 (en) 1993-10-26 1994-10-26 Arrays of nucleic acid probes on biological chips
JP7512811A JPH09507121A (en) 1993-10-26 1994-10-26 Nucleic acid probe array on biological chip
AU81266/94A AU8126694A (en) 1993-10-26 1994-10-26 Arrays of nucleic acid probes on biological chips
DE69433180T DE69433180T2 (en) 1993-10-26 1994-10-26 FIELDS OF NUCLEIC ACID PROBE ON ORGANIC CHIPS
US08/510,521 US7115364B1 (en) 1993-10-26 1995-08-02 Arrays of nucleic acid probes on biological chips
US08/630,427 US6156501A (en) 1993-10-26 1996-04-03 Arrays of modified nucleic acid probes and methods of use
US08/648,709 US6045996A (en) 1993-10-26 1996-05-16 Hybridization assays on oligonucleotide arrays
US08/778,794 US6309823B1 (en) 1993-10-26 1997-01-03 Arrays of nucleic acid probes for analyzing biotransformation genes and methods of using the same
US09/393,389 US6632605B1 (en) 1993-10-26 1999-09-10 Hybridization assays on oligonucleotide arrays
US09/510,378 US7399584B2 (en) 1993-10-26 2000-02-22 Method of comparing a target nucleic acid and a reference nucleic acid
US09/798,260 US20030165830A1 (en) 1993-10-26 2001-03-01 Arrays of nucleic acid probes for analyzing biotransformation genes
US10/113,885 US20030134291A1 (en) 1993-06-25 2002-03-28 Polymorphism detection
US10/229,319 US20030054393A1 (en) 1993-06-25 2002-08-27 Methods for polymorphism identification and profiling
US10/402,333 US20030232361A1 (en) 1993-10-26 2003-03-27 Nucleic acid array preparation using purified phosphoramidites
US10/418,414 US7375198B2 (en) 1993-10-26 2003-04-18 Modified nucleic acid probes
US11/367,800 US20060229824A1 (en) 1993-10-26 2006-03-03 Arrays of nucleic acid probes for analyzing biotransformation genes
US11/388,199 US20060263807A1 (en) 1993-06-25 2006-03-24 Methods for polymorphism identification and profiling
US11/401,482 US7846659B2 (en) 1993-10-26 2006-04-11 Arrays of nucleic acid probes for analyzing biotransformation genes
US11/506,176 US20120329677A9 (en) 1993-10-26 2006-08-18 Arrays of nucleic acid probes for detecting cystic fibrosis
US12/124,061 US7794943B2 (en) 1993-10-26 2008-05-20 Modified nucleic acid probes
US12/878,743 US20110092382A1 (en) 1993-10-26 2010-09-09 Modified Nucleic Acid Probes
US12/959,359 US20130150248A1 (en) 1993-10-26 2010-12-02 Arrays of Nucleic Acid Probes for Analyzing Biotransformation Genes

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US14331293A 1993-10-26 1993-10-26
US28406494A 1994-08-02 1994-08-02
US08/284,064 1994-08-02
US08/143,312 1994-08-02

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
US14331293A Continuation-In-Part 1993-06-25 1993-10-26
US28406494A Continuation-In-Part 1993-06-25 1994-08-02

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US44074295A Continuation-In-Part 1993-10-26 1995-05-10
US08/510,521 Continuation-In-Part US7115364B1 (en) 1993-06-25 1995-08-02 Arrays of nucleic acid probes on biological chips

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WO1995011995A1 WO1995011995A1 (en) 1995-05-04
WO1995011995B1 true WO1995011995B1 (en) 1995-05-18

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PCT/US1994/012305 WO1995011995A1 (en) 1993-06-25 1994-10-26 Arrays of nucleic acid probes on biological chips

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EP (1) EP0730663B1 (en)
JP (1) JPH09507121A (en)
AU (1) AU8126694A (en)
DE (1) DE69433180T2 (en)
WO (1) WO1995011995A1 (en)

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