Methods for Selecting a Collection of Single Nucleotide Polymorphisms

Abstract

The invention relates to the selection of a collection of relevant single nucleotide polymorphisms across a genome to design a nucleic acid probe array. As such, the invention relates to diverse fields impacted by the nature of genetics, including biology, medicine, and medical diagnostics.

1 - 14 . (canceled) 
     
     
         15 . An array comprising probes to genotype the SNPs in said third pool of SNPs. 
     
     
         16 . A computer implemented method for designing a nucleic acid probe array, comprising the steps of:
 (a) providing a screening array comprising a screening probe set for each of a plurality of SNPs in a first set of SNPs, wherein each screening probe set comprises 56 probes;   (b) genotyping a plurality of individuals using the screening array from (a) to obtain a genotyping data set;   (c) defining one or more genotyping metrics that determine the performance of a SNP in a genotyping assay;   (d) identifying a second set of SNPs from the first set of SNPs, wherein SNPs that passed the metrics of (c) in the genotyping step of (b) are selected for the second set of SNPs;   (e) in the second set of SNPs identifying a subset of probes from the 56 probes of the screening probe set for inclusion in a final probe set for each SNP;   (f) assaying performance of the final probe sets identified in (e) and selecting SNPs that meet selected performance criteria for inclusion in a third set of SNPs;   (g) assaying the SNPS in the third set of SNPs for performance for an entropy based set of selection criteria to select SNPs for a fourth set of SNPs;   (h) designing an array comprising final probe sets for each of the SNPs in the fourth probe set; and   (i) outputting the array design in a computer file, a display or a printout.   
     
     
         17 . The method of  claim 16  wherein the SNPs in the first set of SNPs are human SNPs. 
     
     
         18 . An array of the design output in  claim 17 . 
     
     
         19 . The method of  claim 16  wherein the final probe sets comprise at least 12 probes. 
     
     
         20 . An array of the design output in  claim 19 . 
     
     
         21 . A collection of at least 300,000 probes for genotyping a plurality of SNPs,
 wherein each probe is attached to a solid support and arranged in an array in a known or determinable location; wherein the plurality of SNPs comprises at least 300,000 SNPs wherein the mean minor allele frequency for the SNPs in the collection is at least 0.20 and the mean interSNP distance for the plurality of SNPs is less than 10 kb.   
     
     
         22 . The collection of  claim 21  wherein the mean interSNP distance for the plurality of SNPs is less than 8 kb. 
     
     
         23 . The collection of  claim 21  wherein there are more than 400,000 SNPs and the mean interSNP distance for the plurality of SNPs is less than 6 kb. 
     
     
         24 . The collection of  claim 21  wherein the mean heterozygosity is at least 0.25.