POLYMORPHISM DETECTION

• US 20100286924A1
• Filed: 01/25/2010
• Published: 11/11/2010
• Est. Priority Date: 11/29/1995
• Status: Active Grant

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: LIPSHUTZ, ROBERT J., SAPOLSKY, RONALD, GHANDOUR, GHASSAN
• Granted Patent: US 8,095,323 B2
• Time in Patent Office: Days
• US Class Current: 702/19
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• 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: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C12Q 1/6827 for detection of mutation or polymorphism
• 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 2525/185 incorporating bases where the precise position of the bases in the nucleic acid string is important
• CPC Class Codes: C12Q 2525/204 specific length of the oligonucleotides
• 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
• CPC Class Codes: G16B 25/00 ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• CPC Class Codes: G16B 30/00 ICT specially adapted for sequence analysis involving nucleotides or amino acids
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

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, i.e., the heterozygote or either of the two homozygotes. The method allows for rapid, automatable analysis of genetic linkage to even complex polygenic traits

Claims

1-17. -17. (canceled)

18. A computer program product that determines a genotype of a sample of nucleic acid sequences, comprising:

computer code that receives a first hybridization intensity indicating hybridization affinity between a first set of probes and a first allele, the first set of probes being complementary to a portion of the first allele;

computer code that receives a second hybridization intensity indicating hybridization affinity between a second set of probes and the first allele, the second set of probes having a single base mismatch with a portion of the first allele;

computer code that calculates a first difference between the first and second hybridization intensities;

computer code that receives a third hybridization intensity indicating hybridization affinity between a third set of probes and a second allele, the third set of probes being complementary to a portion of the second allele;

computer code that receives a fourth hybridization intensity indicating hybridization affinity between a fourth set of probes and a second allele, the fourth set of probes having a single base mismatch with a portion of the first allele;

computer code that calculates a second difference between the third and fourth hybridization intensities;

computer code that compares the first and second differences in order to determine the genotype of the sample of nucleic acid sequences; and

a computer readable medium that stores said computer codes.

19. The computer program product of claim 18, wherein the computer readable medium is a memory, floppy disk, CD-ROMN, tape or flash memory.