Polymorphism detection

• US 20030134291A1
• Filed: 03/28/2002
• Published: 07/17/2003
• Est. Priority Date: 06/25/1993
• Status: Abandoned Application

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Morris, MacDonald S., Fodor, Stephen P.A., Lipshutz, Robert J., Hubbell, Earl A., Chee, Mark S., Cronin, Maureen T., Miyada, Charles Garrett
• Application Number:
  US10/113,885
• Publication Number:
  US 20030134291A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00695 Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/00711 Light-directed synthesis
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C07B 2200/11 Compounds covalently bound to a solid support
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12Q 1/6827 for detection of mutation or polymorphism
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: C12Q 2525/179 incorporating arbitrary or random nucleotide sequences
• CPC Class Codes: C12Q 2535/131 Allele specific probes
• CPC Class Codes: C12Q 2565/501 being an array of oligonucleotides
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries

Abstract

The present invention generally provides a rapid efficient method for analyzing polymorphic or biallelic markers, and arrays for carrying out these analyses. In general, the methods of the present invention employ arrays of oligonucleotide probes that are complementary to target nucleic acids which correspond to the marker sequences of an individual. The probes are typically arranged in detection blocks, each block being capable of discriminating the three genotypes for a given marker, e.g., the heterozygote or either of the two homozygotes. The method allows for rapid, automatable analysis of genetic linkage to even complex polygenic traits.

Claims

1. An array of oligonucleotide probes for detecting a previously identified polymorphism in a target nucleic acid sequence, said array comprising at least one detection block of probes selected for detection of the previously identified polymorphism said detection block including first and second groups of probes that are complementary to said target nucleic acid sequence having first and second variants of said polymorphism, respectively, and further comprising third and fourth groups of probes, said third and fourth groups of probes having a sequence identical to said first and second groups of probes, respectively, except that said third and fourth groups of probes include all possible monosubstitutions of positions in said sequence that are within n bases of a base in said sequence that is complementary to said polymorphism, wherein n is from 1 to 5.

2. The array of claim 1, wherein n is 2.

3. The array of claim 1, wherein said first and second groups of probes comprise a plurality of different probes that are complementary to overlapping portions of said target nucleic acid sequence including the previously determined polymorphism.

4. The array of claim 1, wherein said monosubstitutions in said first and second groups of probes occur at a plurality of distances from a 3′

end of said probes.

5. The array of claim 1, wherein said detection block includes between about 8 and 88 probes.

6. The array of claim 1, comprising between 1 and 1,000 different detection blocks, each of said detection blocks including probes complementary to first and second variants of a different polymorphism in said target nucleic acid sequence.