Differential sequencing with mass spectrometry

Differential or genetic sequencing requires searching sample DNA for variat ions with respect to a reference sequence. Conventional detection technique s are too labor and cost expensive for use in diagnostic applications, ther efore new technologies will be required. Measurement techniques based on ma ss spectrometry (MS) possess the potential for high-throughput, high fideli ty measurement of sequence variation. Unambiguous detection of polymorphic sequences has been demonstrated, even in heterozygous samples. Automated re producible measurements of microscopic arrays of samples will enable the hi gh-throughput detection required for large-scale applications. Computationa l simulation and analysis of experimental parameters prior to experimentati on will provide the optimization necessary for development of robust, repro ducible measurements. (C) 1999 Elsevier Science B.V. All rights reserved.