Sequence-Based Detection of Single Nucleotide Polymorphisms

One of the major tasks in human genome analysis is the identification and typing of DNA sequence variations (1 ). There are many types of sequence variations in the human genome. One type comprises sequences with variations in the number of repeat units such as short tandem repeat polymorphisms in the form of di-, tri, and tetranucleotide repeats; more complex sequence repeats such as variable number tandem repeats; or variations in the lengths of mononucleotide tracks such as A- or T-tracks in the genome. The other major type of variation in the genome arises from discrete changes in a specific DNA sequence such as small but unique base insertions or deletions, or more frequently as single nucleotide substitutions, also known as single nucleotide polymorphisms (SNPs). SNPs are the most abundant form of DNA sequence variation in the human genome (2 ). Based on their natural frequency and presence in both coding and noncoding regions, single nucleotide substitutions are probably the underlying cause of most phenotypic differences among humans. Therefore, the identification of SNPs in human genes will play an increasingly important role in analyzing genotype-phenotype correlations within and among human populations (2 ). Amplification of genomic DNA by the polymerase chain reaction (PCR) has greatly simplified the identification of SNPs by eliminating the need to clone and isolate regions of the genome from multiple individuals.