High resolution chromosomal mapping

• US 8,058,055 B2
• Filed: 04/07/2006
• Issued: 11/15/2011
• Est. Priority Date: 04/07/2006
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Barrett, Michael Thomas, Caren, Michael P.
• Primary Examiner(s): Pohnert; Steven
• Assistant Examiner(s): BHAT, NARAYAN KAMESHWAR
• Application Number:
  US11/400,481
• Publication Number:
  US 20070238105A1
• Time in Patent Office: 2,048 Days
• Field of Search: 435/6, 435/287.2, 536/23.1, 536/24.33
• US Class Current: 435/287.2
• CPC Class Codes: C12Q 1/6841 In situ hybridisation

Abstract

The present invention generally relates to spatial and structural genomic analysis compositions, which can be used for the mapping of chromosomes and structural analyses of chromosomal rearrangements, including the entire chromosome, as well as specific portions or regions of interest of the chromosomes. In some embodiments, multiple portions of the genome can be distinguished, for instance, using a first detection entity and a second detection entity different from the first detection entity. The detection entities may be immobilized relative to oligonucleotides, which may be selected to bind to different locations within the chromosome. For instance, the oligonucleotides may be at least substantially complementary to the chromosome, e.g., substantially complementary to a specific location of the chromosome.

Claims

1. A composition comprising:

a solution comprising a mixture of at least 5 different labeled oligonucleotides that all specifically bind to a region in a mammalian chromosome,

wherein said labeled oligonucleotides are in solution;

wherein said labeled oligonucleotides are complementary to a unique sequence in said region and are of 80 to 200 nucleotides in length; and

wherein said labeled oligonucleotides comprise a nucleotide sequence that overlaps with the nucleotide sequence of another labeled oligonucleotide in said mixture such that said labeled oligonucleotides, when hybridized to said mammalian chromosome, are tiled across said region.

2. The composition of claim 1, wherein said solution further comprises labeled oligonucleotides that bind to said region and do not overlap with another labeled oligonucleotide in said mixture.

3. The composition of claim 1, wherein said oligonucleotides comprise a PCR primer sequence.

4. The composition of claim 1, wherein said oligonucleotides comprise a restriction endonuclease cleavage site.

5. The composition of claim 1, wherein said oligonucleotides are synthesized on a solid support in an array, cleaved from said array, and then labeled.

6. A kit for use within an assay of a nucleic acid to physically analyze the nucleic acid, the kit comprising:

a mixture of at least 5 different labeled oligonucleotides that all specifically bind to a region in a mammalian chromosome,

wherein said labeled oligonucleotides are in solution;

wherein said labeled oligonucleotides are complementary to a unique sequence in said region and are of 80 to 200 nucleotides in length; and

wherein said labeled oligonucleotides comprise a nucleotide sequence that overlaps with the nucleotide sequence of another labeled oligonucleotide in said mixture such that said labeled oligonucleotides, when hybridized to said mammalian chromosome, are tiled across said region.

7. The kit of claim 6, wherein said mixture further comprises labeled oligonucleotides that bind to said region and do not overlap with another labeled oligonucleotide in said mixture.