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Single-Nucleotide Polymorphism Genotyping for Disease Association Studies

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The Human Genome Project has led to the discovery of millions of DNA sequence variants in the human genome. The majority of these variants are single-nucleotide polymorphisms (SNPs). Availability of an ultra-high-density SNP map, combined with improvement in genotyping technologies and efficient analytical approaches, opens the possibility of fulfilling the promise of SNP association studies to reveal why some individuals are more susceptible to common chronic diseases such as hypertension and stroke. With millions of SNPs spread throughout the human genome, it is neither practical nor necessary to genotype every single SNP in population samples for association studies. Linkage disequilibrium between sites suggests that it is possible to detect disease association using a relatively sparse collection of SNPs. While the cost associated with assaying a comprehensive set of SNPs is still significant, several technologies show great promise for high-efficiency SNP genotyping. This chapter focuses on two of them: the 5′-nuclease assay and mass spectrometry genotyping.
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