Clinical Chemistry
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Clinical Chemistry 43: 1108-1109, 1997;
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(Clinical Chemistry. 1997;43:1108-1109.)
© 1997 American Association for Clinical Chemistry, Inc.

Editorials

Mass-Spectrometric Approaches for DNA-Based Genetic Screening

Gregg B. Fields

University of Minnesota Medical School, Department of Laboratory Medicine & Pathology, Box 107, 420 Delaware St., SE, Minneapolis, Minnesota 55455, Fax 612-625-1121, E-mail field002@maroon.tc.umn.edu

In the current issue of Clinical Chemistry, Braun et al. (1) describe a mutational analysis method that combines primer oligo base extension (PROBE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). This application further extends the use of MS for genetic analysis and suggests a possible role in the clinic. However, what is the long-term potential for MALDI, based on the relative strengths and weaknesses of MS analysis of DNA (2)?

The development of soft-ionization techniques for MS has, without question, revolutionized protein chemistry. MS is now one of the definitive methods for characterization of synthetic and isolated peptides and proteins. In addition to accurately determining an intact mass, one can obtain primary structure information by several different MS sequencing strategies, and secondary and tertiary structure can be evaluated by hydrogen-exchange experiments. The use of MS for DNA analysis, although first demonstrated for nucleosides in 1962 (3), is far less advanced. Potential applications of MS are (a) detection of DNA modifications, (b) DNA fragment mass determination, and (c) DNA sequencing. Both fast atom bombardment (FAB) and electrospray ionization (ESI) collision-induced dissociation/tandem MS have been applied for identification of DNA modification sites. For example, the carcinogen N-nitrosopiperidine reacts . . . [Full Text of this Article]


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Copyright © 1997 by the American Association for Clinical Chemistry.