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SNP genotyping with arrays

Single nucleotide polymorphisms (SNPs) are sequence variants in which two alternate bases occur at one position. The SNP Consortium is developing a dense map of SNPs in the hope that certain variants can be associated with disease states. With hundreds of thousands of SNPs identified, the scoring of these SNPs in patient populations has become the limiting factor. Hirschhorn et al. provide a possible solution in the October 24 Proceedings of the National Academy of Sciences by making the existin

By | October 19, 2000

Single nucleotide polymorphisms (SNPs) are sequence variants in which two alternate bases occur at one position. The SNP Consortium is developing a dense map of SNPs in the hope that certain variants can be associated with disease states. With hundreds of thousands of SNPs identified, the scoring of these SNPs in patient populations has become the limiting factor. Hirschhorn et al. provide a possible solution in the October 24 Proceedings of the National Academy of Sciences by making the existing technique of single-base extension (SBE) a parallel process (Proc Natl Acad Sci USA 2000, 97:12164-12169). The technique begins with target amplification and the annealing of a primer next to a SNP site. A single fluorescently labeled nucleotide is incorporated as the next base; the identity of the fluorescent label identifies the variant base. Hirschhorn et al. modify this basic SBE technique by adding generic sequence tags to the primers. Up to 100 of the primer/tag combinations are added to a single sample and, following SBE, annealed to a spotted array of anti-tag oligonucleotides on a glass slide. All the SNP results can be read out simultaneously with an accuracy of approximately 99%. The technique is cheaper than a similar version based on photolithography, and more versatile than a version that requires arrays of locus-specific primers.

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