Abstract

Abstract This chapter introduces the use of matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry for high-throughput comparative sequence analysis. We first briefly define the concept of comparative sequence analysis in the context of current genomic and genetic research. The chapter then summarizes the basic principles and challenges of MALDI-TOF mass spectrometry (MS) of nucleic acids and introduces the concept of base-specific cleavage analyzed by MALDI-TOF MS for discovery of sequence changes. We provide an overview of how the concept applies to some of the predominant research questions in genomics and genetics, such as discovery of new mutations, analysis of cytosine methylation or rapid identification and characterization of pathogenic organisms. Finally, we provide an outlook of further developments, which will significantly expand the capability and performance of the introduced methods and concept.

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