Patent ID: 7634363
Filing Date: 2009-12-15
Classification: C12Q,G16B

Abstract:
1. A method for calling the genotype of a sample at a selected polymorphism in a sample using a genotyping array, comprising: (a) obtaining intensity measurements for allele A and for allele B for a plurality of polymorphisms in a plurality of training samples, wherein the genotype of each polymorphism in the plurality in each training sample is of known genotype, wherein the intensity measurements represent intensity of signal associated with one or more features on said genotyping array; (b) making a genotype call for each of a said polymorphisms in each of the training samples using the intensity measurements for allele A and for allele B obtained in (a); (c) comparing the genotype call with the known genotype to identify individuals where the correct genotype call was made; (d) using the intensity measurements from the individuals identified in (c) to calculate a ratio of intensity measurement for allele A to intensity measurement for allele B, for the training samples for each sub-group of AA, AB and BB to obtain an AA reference ratio, an AB reference ratio and a BB reference ratio for each of said polymorphisms; (e) hybridizing a test sample to the genotyping array to obtain hybridization intensity values for the A allele and for the B allele for each of said polymorphisms in the test sample; (f) calculating a ratio of the intensity measurement for the A allele to the B allele for each of said polymorphisms in the test sample and comparing the ratio to the reference ratios for AA, AB and BB obtained for that polymorphism in (d) to determine the likelihood that the polymorphism is AB; (g) identifying a subset of the polymorphisms in the test sample that are likely to be AB, wherein a polymorphism is identified as being likely to be AB if the likelihood that the polymorphism is AB is greater than a selected threshold; (h) adjusting the intensity measurement of the B allele by the reference ratio for the AB group for that polymorphism from the training set to obtain an adjusted intensity measurement for the B allele, for each polymorphism in the subset of polymorphisms identified in (g); and (i) generating a genotype call for each of the polymorphisms identified in (g) using the adjusted intensity measurement for the B allele.