European Journal of Pediatrics

, Volume 162, Supplement 1, pp S13–S16 | Cite as

Technology challenges in screening single gene disorders

  • Andreas Braun
  • Richard Roth
  • Matthew J. McGinniss


The completion of the human genome project and the accelerated discovery of genes responsible for single gene disorders will allow for the preventive screening of carriers and patients. Accuracy and reliability of analytic tests are major demands on technologies used in a diagnostic screening environment. The consistency of results and the potential of multiplexing suggest mass spectrometry as the method of choice for large-scale genetic screening programs. The added ability to analyze other large molecules such as peptides and proteins further underlines the versatility and usefulness of this technology. We describe the use of mass spectrometry for screening of sickle cell disease at the level of DNA and protein. Conclusion:analytic methods are needed for large-scale screening and diagnostic applications that are highly accurate, fully automated and cost-effective. The precise measurement of molecular weights and the use of high fidelity enzymes to produce diagnostic products make mass spectrometry the method of choice for DNA and protein screening procedures.


Carrier testing External quality assessment Genetic screening Mass spectrometry 



matrix assisted laser desorption ionization—time of flight mass spectrometry


single nucleotide polymorphism


  1. 1.
    Braun A, Little DP, Koester H (1997) Detecting CFTR gene mutations by using primer oligo base extension and mass spectrometry. Clin Chem 43: 1151–1158PubMedGoogle Scholar
  2. 2.
    Buetow KH, Edmonson M, MacDonald R, Clifford R, Yip P, Kelley J, Little DP, Strausberg R, Koester H, Cantor CR, Braun A (2001) High-throughput development and characterization of a genome-wide collection of gene-based single nucleotide markers by chip-based matrix-assisted laser desorption / ionization time-of-flight mass spectrometry. PNAS 98: 581–584CrossRefPubMedGoogle Scholar
  3. 3.
    Charrow J, Goodman SI, McCabe ERG, Rinaldo P (2000) ACMG/ASHG Statement. Tandem mass spectrometry in newborn screening. Genet Med 2: 267–269PubMedGoogle Scholar
  4. 4.
    Dequeker E, Cassiman JJ (2000) Genetic testing and quality control in diagnostic laboratories. Nat Genet 25: 259–260PubMedGoogle Scholar
  5. 5.
    Dequeker E, Ramsden S, Grody WW, Stenzel TT, Barton DE (2001) Quality control in molecular genetic testing. Nat Rev Genet 2: 717–723PubMedGoogle Scholar
  6. 6.
    Kaback MM (2000) Population-based genetic screening for reproductive counseling: the Tay-Sachs disease model. Eur J Pediatr 159[Suppl 3]: S192–S195Google Scholar
  7. 7.
    McGovern MM, Benach MO, Wallenstein S, Desnick RJ, Keenlyside R (1999) Quality assurance in molecular genetic testing laboratories. JAMA 281: 835–840PubMedGoogle Scholar
  8. 8.
    Weatherall DJ, Clegg JB (2001) Inherited haemoglobin disorders: an increasing global health problem. Bull World Health Org 79: 704–712PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Andreas Braun
    • 1
  • Richard Roth
    • 1
  • Matthew J. McGinniss
    • 1
  1. 1.SEQUENOM Inc.San Diego USA

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