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Constant denaturant capillary electrophoresis (CDCE) separates macromolecules based on differences in their melting temperatures. The specific apparatus and operating conditions have been described previously that allow CDCE to separate point mutants among100-150-bp iso-melting
DNA
sequences (
1
,
2
). CDCE coupled with high-fidelity DNA polymerase chain reaction (
PCR
) has been applied to the measurement of point mutationalspectra in human cell and tissue samples (
3
-
4
). For reviews of this field
seerefs.7
,
8
. This chapter describes additional techniques which when combined with CDCE and high-fidelity PCR allow point mutation detectionat fractions as low as 10
−6
.