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        SNP Discovery by Direct DNA Sequencing

        互联网

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        DNA sequencing, while relatively laborious, is the gold standard in mutation detection and single nucleotide polymorphism (SNP) discovery. The most widely used approach is direct DNA sequencing of polymerase chain reaction (PCR) products with dye-terminator chemistry analyzed on automated DNA sequencers (1 ). Although the quality of DNA sequencing data has improved significantly over the last few years, the peak pattern remains uneven and random artifacts are seen from time to time (2 ). Because human cells are diploid, DNA sequence of a heterozygote contains a locus where two different bases occupy the same site. The uneven peak pattern makes it difficult sometimes to discern these composite peaks because one of the two polymorphic bases may be disproportionately smaller than the other base and the base-calling algorithm of the automatic DNA sequencer misses the correct call (2 4 ).
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