Patent ID: 7424368

Claim:
A method for estimating the copy number of a genomic region in an experimental sample comprising: (a) isolating nucleic acid from the experimental sample; (b) amplifying at least some regions of the nucleic acid; (c) labeling the amplified products; (d) hybridizing the labeled amplified products to an array to obtain a hybridization pattern, wherein the array comprises a plurality of genotyping probe sets for a plurality of SNPs comprising autosomal SNPs, wherein a probe set comprises: (i) a plurality of perfect match probes to a first allele of a SNP, (ii) a plurality of perfect match probes to a second allele of the SNP, (iii) a plurality of mismatch probes to the first allele of the SNP, and (iv) a plurality of mismatch probes to the second allele of the SNP, (e) obtaining a measurement for the SNP in the experimental sample wherein the measurement, S, is the log of the arithmetic average of the intensities of at least two of the perfect match probes to said first allele or at least two of the perfect match probes to said second allele for the SNP in the hybridization pattern normalized to the S values of all SNPs genotyped in the experimental sample; (f) obtaining an S value for the SNP in each of a plurality of reference samples that are matched to the experimental sample in genotype call at the SNP, wherein the S value is the log of the average of the intensities of at least two perfect match probes in a reference hybridization pattern normalized to the S values of all SNPs genotyped in that reference sample; (g) calculating the mean for the reference sample S values using the values obtained in (f); (h) obtaining a log intensity difference by subtracting the mean value obtained in (g) from the value of the measurement, S, obtained in (e); and (i) estimating the copy number of the region including the SNP wherein copy number is estimated using: Copy Number≅exp( b+m ×({tilde over ( S )} jg C −{circumflex over (μ)} jg )) wherein {tilde over (S)} jg C is the log of the average of the intensities of the perfect match probes for a SNP j of genotype g in an experimental sample c, normalized to the S values of all SNPs genotyped in the experimental sample, {circumflex over (μ)} jg is the mean of the S values for SNP j in a plurality of reference samples of genotype g at SNP j, b is the y-intercept and m is the slope of a line defined by plotting intensity values from SNPs of known copy number and obtaining from the estimated copy number an estimated copy number alteration and an estimated direction of copy number change.