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MALDI Mass Spectrometry for Nucleic Acid Analysis

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Applications of MALDI-TOF Spectroscopy

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 331))

Abstract

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.

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Abbreviations

3-HPA:

3-Hydroxypicolinic acid

ATT:

6-Aza-2-thiothymine

ddNTP:

Dideoxynucleotide triphosphate

FFPE:

Formalin-fixed paraffin-embedded

MALDI-MS:

Matrix-assisted laser desorption/ionization mass spectrometry

MLEE:

Multilocus enzyme electrophoresis

MLST:

Multilocus sequence typing

m/z :

Mass to charge ratio

SNP:

Single nucleotide polymorphism

tRNA:

Transfer RNA

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Acknowledgements

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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Authors and Affiliations

  1. Division of Chemical Biology and Biotechnology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore

    Xiang Gao & Kai Tang

  2. Detection and Diagnostic Laboratory, DSO National Laboratories, Singapore, Singapore

    Boon-Huan Tan

  3. Division of Molecular and Cellular Biology, School of Biological Sciences, Nanyang Technological University, Singapore, Singapore

    Richard J. Sugrue

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  1. Xiang Gao
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  2. Boon-Huan Tan
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  3. Richard J. Sugrue
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  4. Kai Tang
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Correspondence to Kai Tang .

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Editors and Affiliations

  1. , Department of Chemistry, Hong Kong Baptist University, Ho Sin Hang Campus, Hong Kong, 000000000, China, People's Republic

    Zongwei Cai

  2. , Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 000000000, China, People's Republic

    Shuying Liu

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Gao, X., Tan, BH., Sugrue, R.J., Tang, K. (2012). MALDI Mass Spectrometry for Nucleic Acid Analysis. In: Cai, Z., Liu, S. (eds) Applications of MALDI-TOF Spectroscopy. Topics in Current Chemistry, vol 331. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2012_366

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