MALDI Mass Spectrometry for Nucleic Acid Analysis

  • Xiang Gao
  • Boon-Huan Tan
  • Richard J. Sugrue
  • Kai TangEmail author
Part of the Topics in Current Chemistry book series (TOPCURRCHEM, volume 331)


With the discovery of several matrices which enable the ionization of DNA and RNA, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has become a powerful platform for the study of nucleic acid sequence changes (e.g., mutations, single nucleotide polymorphisms (SNPs), insertion/deletion, alternative splicing, etc.), amount changes (e.g., copy number variation, gene expression, allele expression, etc.), as well as modifications (e.g., methylation of genomic DNA, post transcriptional modification of tRNAs and rRNAs). Two major strategies have been employed to characterize these changes. Primer extension reactions are designed for genotyping of known polymorphic sites and determining the levels of gene or allele expressions. Base-specific cleavage reactions are used for discovery of unknown polymorphisms and characterization of modifications. These two assays usually generate nucleic acid fragments less than 30 bases in length, which is the ideal mass range for MALDI-MS. Here we review the basic concepts of these assays, sample analysis techniques, and their applications published in recent years.


Base-specific cleavage Comparative sequencing MALDI-MS Nucleic acids Primer extension SNP 



3-Hydroxypicolinic acid




Dideoxynucleotide triphosphate


Formalin-fixed paraffin-embedded


Matrix-assisted laser desorption/ionization mass spectrometry


Multilocus enzyme electrophoresis


Multilocus sequence typing


Mass to charge ratio


Single nucleotide polymorphism


Transfer RNA



KT is supported by Ministry of Health of Singapore, BHT by the Ministry of Defense, and RJS by Ministry of Health of Singapore, National Research Foundation, and Defense Science & Technology Agency.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Xiang Gao
    • 1
  • Boon-Huan Tan
    • 2
  • Richard J. Sugrue
    • 3
  • Kai Tang
    • 1
    Email author
  1. 1.Division of Chemical Biology and Biotechnology, School of Biological SciencesNanyang Technological UniversitySingaporeSingapore
  2. 2.Detection and Diagnostic Laboratory, DSO National LaboratoriesSingaporeSingapore
  3. 3.Division of Molecular and Cellular Biology, School of Biological SciencesNanyang Technological UniversitySingaporeSingapore

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