Comparative fluorescence hybridization to nucleic acid arrays
First Claim
Patent Images
1. A method for comparing copy number of nucleic acid sequences in two or more collections of nucleic acid molecules, the method comprising:
- (a) providing an array comprising a plurality of target elements bound to a solid surface, each target element comprising a target nucleic acid, which target nucleic acid is not in a cell nucleus and lacks superstructure of a condensed chromosome;
(b) contacting the target elements with;
(i) a first collection of labeled nucleic acid molecules comprising a plurality of first nucleic acid sequences each of which specifically hybridizes to a different target nucleic acid under pre-selected hybridization conditions, and (ii) a second collection of labeled nucleic acid molecules comprising a plurality of second nucleic acid sequences each of which specifically hybridizes to a different target nucleic acid under pre-selected hybridization conditions;
wherein the first and second labels are distinguishable from each other and at least one of the first and at least one of the second nucleic acid sequences hybridize to the same target nucleic acid;
(c) detecting the amount of binding of the first and second labeled complementary nucleic acids to the target nucleic acids; and
(d) comparing the amount of binding of the first and second labeled complementary nucleic acids to the target nucleic acids to compare copy number of nucleic acid sequences in the first and second collections that are bound to the target nucleic acids.
1 Assignment
0 Petitions
Accused Products
Abstract
The present invention provides methods of determining relative copy number of target nucleic acids and precise mapping of chromosomal abnormalities associated with disease. The methods of the invention use target nucleic acids immobilized on a solid surface, to which a sample comprising two sets of differentially labeled nucleic acids are hybridized. The hybridization of the labeled nucleic acids to the solid surface is then detected using standard techniques.
-
Citations
29 Claims
-
1. A method for comparing copy number of nucleic acid sequences in two or more collections of nucleic acid molecules, the method comprising:
-
(a) providing an array comprising a plurality of target elements bound to a solid surface, each target element comprising a target nucleic acid, which target nucleic acid is not in a cell nucleus and lacks superstructure of a condensed chromosome;
(b) contacting the target elements with;
(i) a first collection of labeled nucleic acid molecules comprising a plurality of first nucleic acid sequences each of which specifically hybridizes to a different target nucleic acid under pre-selected hybridization conditions, and (ii) a second collection of labeled nucleic acid molecules comprising a plurality of second nucleic acid sequences each of which specifically hybridizes to a different target nucleic acid under pre-selected hybridization conditions;
wherein the first and second labels are distinguishable from each other and at least one of the first and at least one of the second nucleic acid sequences hybridize to the same target nucleic acid;
(c) detecting the amount of binding of the first and second labeled complementary nucleic acids to the target nucleic acids; and
(d) comparing the amount of binding of the first and second labeled complementary nucleic acids to the target nucleic acids to compare copy number of nucleic acid sequences in the first and second collections that are bound to the target nucleic acids. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 25)
-
-
24. A method of comparing copy number of nucleic acid sequences in two or more collections of nucleic acid molecules, the method comprising:
-
(a) providing an array comprising a plurality of target elements bound to a solid surface, each target element comprising a target nucleic acid, which target nucleic acid is not in a cell nucleus and lacks superstructure of a condensed chromosome;
(b) contacting the target elements with;
(i) a first collection of fluorescently labeled nucleic acid molecules comprising a plurality of first nucleic acid sequences each of which specifically hybridizes to a different target nucleic acid under pre-selected hybridization conditions, and (ii) at least a second collection of fluorescently labeled nucleic acid molecules comprising a plurality of second nucleic acid sequences each of which specifically hybridizes to a different target nucleic acid under pre-selected hybridization conditions;
wherein the first and second labels are distinguishable from each other and at least one of the first and at least one of the second nucleic acid sequences hybridize to the same target nucleic acid;
(c) detecting the amount of binding of the first and second labeled complementary nucleic acids to the target nucleic acids; and
(d) comparing the amount of binding of the first and second labeled complementary nucleic acids to the target nucleic acids to compare copy number of nucleic acid sequences in the first and second collections that are bound to the target nucleic acids. - View Dependent Claims (26, 27, 28)
-
-
29. A method for comparing the relative copy numbers of nucleic acid sequences in a plurality of collections of nucleic acid molecules, the method comprising:
-
(a) providing an array comprising a plurality of target elements bound to a solid surface, each target element comprising a target nucleic acid, which target nucleic acid is not in a cell nucleus and lacks superstructure of a condensed chromosome;
(b) contacting the target elements with;
(i) a first collection of labeled nucleic acid molecules comprising a plurality of first nucleic acid sequences each of which specifically hybridizes to a different target nucleic acid under pre-selected hybridization conditions, and (ii) a second collection of labeled nucleic acid molecules comprising a plurality of second nucleic acid sequences each of which specifically hybridizes to a different target nucleic acid under pre-selected hybridization conditions;
wherein the first and second labels are distinguishable from each other, and wherein a plurality of the first and a plurality of the second nucleic acid sequences hybridize to the same target nucleic acids;
(c) detecting the first and second labels bound to each of a plurality of said target elements to determine, for each of such target elements, the binding ratio of the first and second nucleic acid sequences bound thereto; and
(d) comparing a plurality of said binding ratios with one another to determine the relative copy numbers of nucleic acid sequences in said first and second collections that are bound to such target elements.
-
Specification