Methods for Genotyping Polymorphisms
The invention provides method for genotyping specific sets of polymorphisms in a single multiplex reaction. The polymorphisms are selected to be of interest in detecting genetic variation that alters individuals' metabolism, distribution, extretion and transport of pharmacological compounds. In preferred aspects the genotyping employs a multiplex hybridization-based assay. In some aspects combinations of methods are employed to allow the combination of polymorphisms to be interrogated. The invention also provides nucleic acid standards for validating the performance of such hybridization-based assays.
1 . A method of determining a patient's risk for an adverse drug response comprising:
(a) genotyping the patient for each of the SNPs in Table 6 to obtain the patient's genotype for each of the SNPs in Table 6;
(b) comparing the genotype of the patient at each of a plurality of the SNPs in Table 5 to a table of genotypes for each of the SNPs listed in Table 6, wherein each of the genotypes in the table of genotypes is associated with a risk for an adverse drug response to one or more drugs selected from a plurality of drugs; and
(c) determining the patient's risk for an adverse drug response to a drug from said plurality of drugs.
2 . The method of claim 1 wherein said genotyping is by a method comprising: hybridizing a padlock probe to a DNA sample from said patient; ligating the ends of the padlock probe in a sequence dependent manner to form a closed circle probe; amplifying the closed circle probe to obtain an amplification product and detecting the presence of the amplification product.
3 . The method of claim 2 wherein the step of detecting comprises hybridization to an array of probes that are complementary to tag sequences that are present in the padlock probe and wherein padlock probes for different SNPs comprise different specific tag sequences that can be used to identify the individual SNPs.
4 . The method of claims 1 , 2 or 3 further comprising (i) genotyping the patent for at least 100 SNPs in Table 5 and (ii) repeating steps (b) and (c) for the at least 100 SNPs in Table 5 that were genotyped in step (i).