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Julie Chang, Bio-Rad Laboratories, Inc., 2000 Alfred Nobel Drive, Hercules, CA 94547
Introduction
Capillary sequencing technology has altered the field of genomics, increasing
throughput and automating the sequencing process. This high-throughput
platform has become a standard in production laboratories, driving such
achievements as the completion of the Human Genome Project.
One of the requirements for achieving this higherthroughput processing is high sample purity. Samples must be free of unincorporated dye terminators and other contaminants, including salt.
Achieving a High-Quality Sequence
Many factors besides sample cleanup contribute to a highquality sequence
read. It is essential to start with a pure template that has been prepared
using a reliable method. Poorly prepared template will result in poor
sequencing results, including low signal strengths, short reads, and dye
blob retention. It is also important to use the proper amounts of reagents
in cycle sequencing reactions. Too much or too little template or primer
may result in reads that are difficult to interpret and analyze. Another
factor to be aware of is the use of optimized cycling parameters proper
annealing temperatures, cycle times, cycle numbers, etc. Finally, instrument
error can be minimized through proper matrix installation, fresh polymer,
and clean and unclogged capillaries. These guidelines will help to increase
the likelihood of a high-quality sequence.
Evaluation of Kits
Four parameters relevant to the evaluation of dye terminator cleanup kits
will be discussed: signal intensity, Phred analysis, dye blob removal,
and cost. A total of five 96- well
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