Methods for genomic analysis

• US 6,969,589 B2
• Filed: 03/26/2002
• Issued: 11/29/2005
• Est. Priority Date: 03/30/2001
• Status: Expired due to Term

• Current Assignee: Genetic Technologies Limited
• Original Assignee: Perlegen Sciences, Inc.
• Inventors: Berno, Anthony J., Hinds, David A., Patil, Nila, Cox, David R.
• Primary Examiner(s): Horlick, Kenneth R.
• Assistant Examiner(s): Lu, Frank
• Application Number:
  US10/106,097
• Publication Number:
  US 20030099964A1
• Time in Patent Office: 1,344 Days
• Field of Search: 435/6, 435/91.1, 435/91.2, 435/183, 436/24, 536/23.1, 536/24.3, 536/24.33, 536/25.3
• US Class Current: 435/6.16
• CPC Class Codes: C12Q 1/6827 for detection of mutation or polymorphism
• CPC Class Codes: G16B 30/00 ICT specially adapted for sequence analysis involving nucleotides or amino acids
• CPC Class Codes: G16B 40/00 ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• CPC Class Codes: G16B 40/10 Signal processing, e.g. from mass spectrometry [MS] or from PCR
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

Abstract

The present invention relates to methods for identifying variations that occur in the human genome and relating these variations to the genetic basis of disease and drug response. In particular, the present invention relates to identifying individual SNPs, determining SNP haplotype blocks and patterns, and, further, using the SNP haplotype blocks and patterns to dissect the genetic bases of disease and drug response. The methods of the present invention are useful in whole genome analysis.

Claims

1. A method for selecting SNP haplotype patterns, comprising:

(a) isolating a set of substantially identical nucleic acid strands from a plurality of different origins for analysis;

(b) determining more than one SNP location in each nucleic acid strand in said set;

(c) identifying SNP locations that are linked in said nucleic acid, wherein said SNP locations that are linked form a SNP haplotype block, thereby identifying said SNP haplotype block;

(d) identifying isolate SNP haplotype blocks;

(e) identifying SNP haplotype patterns that occur in the SNP haplotype block identified in step (c) and the isolate SNP haplotype blocks identified in step (d); and

(f) selecting each identified SNP haplotype pattern that occurs in at least two of said substantially identical nucleic acid strands in said set.

2. The method of claim 1, wherein said identifying SNP locations that are linked is determined by a greedy algorithm or a shortest-paths algorithm.

3. The method of claim 1, wherein at least one or more SNP haplotype blocks axe identified in step (c), and said at least one or more SNP haplotype blocks identified in step (c) and said isolate SNP haplotype blocks are non-overlapping.

4. The method of claim 1, wherein said plurality of different origins is at least between about 10 to about 100 different origins.

5. The method of claim 4, wherein said plurality of different origins is at least about 16 different origins.

6. The method of claim 5, wherein said plurality of different origins is at least about 25 different origins.

7. The method of claim 6, wherein said plurality of different origins is at least about 50 different origins.

8. The method of claim 1, wherein at least two of said substantially identical nucleic acid strands are genomic DNA strands.

9. The method of claim 1, wherein at least a one of the plurality of different origins comprises at least ten percent of genomic DNA from an organism.

10. The method of claim 1, wherein at least 1×

10⁸ bases from at least two of said substantially identical nucleic acid strands are isolated and analyzed.

11. The method of claim 1, wherein selected repeat regions from at least two of said substantially identical nucleic acid strands are not analyzed.

12. The method of claim 1, further comprising:

after said determining of step (b), excluding from analysis those SNP locations that are characterized by an allele that occurs only once in said set of substantially identical nucleic acid strands.

13. A method for selecting a SNP haplotype block useful in genomic analysis, comprising:

isolating a set of substantially identical DNA strands from at least about five different origins for analysis;

analyzing at least about 1×

10⁶ bases from each of said substantially identical DNA strands in said set;

determining more than one SNP location in each of said substantially identical DNA strands in said set;

identifying SNP locations that are linked in said set of substantially identical DNA strands, wherein said SNP locations that are linked form a SNP haplotype block;

identifying SNP haplotype patterns that occur in said SNP haplotype block; and

selecting each identified SNP haplotype pattern that occurs in any of said substantially identical DNA strands in said set.