Single nucleotide polymorphisms (SNPs) represent an abundant and useful source of genetic markers to understand complex diseases. SNPs in coding regions (cSNPs) of biologically important genes are likely to functionally alter the protein product. We have investigated the variability in DNA sequence in 80 genes related to cancer including oncogenes, tumor suppressor genes, and genes involved in cell cycle control. Primer pairs amplifying each exon and intron boundary were designed and used to amplify DNA from four European Americans (CEPH family parents), four African Americans, and four Asian American samples. A total of 72 variants have been characterized. In order to perform high throughput genotyping of cancer gene SNPs we have established 5' nuclease (TaqMan) assays for known variants in drug metabolizing enzymes, hormone receptor genes, immune response genes and chemokines and their receptors. Over 75 assays have been designed and 55 have been tested and found to give accurate genotypes. These variants have been genotyped on cohorts of African American breast cancer, Caucasian lung cancer and Chinese lung cancer patients. Methods to use multiple variants in the same gene to estimate haplotype frequencies have also been tested and shown to give accurate estimations. This will allow detailed analysis of individual genes to be pursued.
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