Summary
Matrix-associated laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is a tool currently under investigation for use in prenatal detection of abnormalities in chromosome number, such as trisomy 21. Because of its ability to detect extremely small differences in mass, even to the level of a single nucleotide difference, this method can be applied to the detection of single-nucleotide polymorphisms (SNPs), which when present in a heterozygous state, can yield quantitative information regarding chromosome status from diagnostic specimens such as amniotic fluid or chorionic villus samples. MALDI-TOF mass spectrometry has several potential advantages over traditional karyotyping methods, including its amenability to high-throughput analyses and its nonreliance on prior cell culture. The method described here is based on the MassEXTEND® protocol developed by Sequenom, Inc., although any mass spectrometry platform sensitive enough to detect the small difference in mass between SNPs could be applied for this purpose.
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References
Gardner, R. J. M. and Sutherland, G. R. (1996) Pregnancy loss and infertility. In: Chromosome abnormalities and genetic counseling, vol 29. Oxford University Press, New York, 311–321.
Dudarewicz, L., Holzgreve, W., Jeziorowska, A., Jahnbowski, L., and Zimmermann, B. (2005) Molecular methods for rapid detection of aneuploidy. J. Appl. Genet. 46, 207–215.
Verma, L., Macdonald, F., Leedham, P., Marton, T., Quirke, P., and Papp, Z. (1998) Rapid and simple prenatal DNA diagnosis of Down’s syndrome. Lancet 352, 9–12.
Findlay, I., Toth, T., Matthews, P., Marton, T., Quirke, P., and Papp. Z. (1998) Rapid trisomy diagnosis (21, 18, and 13) using fluorescent PCR and short tandem repeats: applications for prenatal diagnosis and preimplantation genetic diagnosis. J. Assist. Reprod. Genet. 15, 266–275.
Levett, L. J., Liddle, S., and Meredith, R. (2001) A large-scale evaluation of amnio-PCR for the rapid prenatal diagnosis of fetal trisomy. Ultrasound. Obstet. Gynecol. 17, 115–118.
Mansfield, E. S. (1993) Diagnosis of Down syndrome and other aneuploidies using quantitative polymerase chain reaction and small tandem repeat polymorphisms. Hum. Mol. Genet. 2, 43–50.
Pertl, B., Kopp, S., Kroisel, P. M., et al. (1997) Quantitative fluorescence polymerase chain reaction for the rapid prenatal detection of common aneuoploidies and fetal sex. Am. J. Obstet. Gynecol. 117, 899–906.
Wang, D. G., Fan, J. B., Siao, C. J., et al. (1998) Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science 280, 1077–1082.
Tsui, N. B. Y., Chiu, R. W. K., Ding, C., et al. (2005) Detection of trisomy 21 by quantitative mass spectrometric analysis of single-nucleotide polymorphisms. Clin. Chem. 51, 2358–2362.
Huang D. J., et al. (2006) Reliable detection of trisomy 21 using MALDI-TOF mass spectrometry. Genet. Med. 8, 728–784.
Chiu, C. M. and Muddiman, D. C. (2001)What is Mass Spectrometry? (www.asms.org). American Society for Mass Spectrometry.
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© 2008 Humana Press, a part of Springer Science+Business Media, LLC
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Huang, D.J., Nelson, M.R., Holzgreve, W. (2008). MALDI-TOF Mass Spectrometry for Trisomy Detection. In: Hahn, S., Jackson, L.G. (eds) Prenatal Diagnosis. Methods in Molecular Biology™, vol 444. Humana Press. https://doi.org/10.1007/978-1-59745-066-9_9
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DOI: https://doi.org/10.1007/978-1-59745-066-9_9
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