MS analysis of single-nucleotide differences in circulating nucleic acids: application to noninvasive prenatal diagnosis

Ding, C.M.; Chiu, R.W.K.; Lau, T.K.; Leung, T.N.; Chan, L.C.; Chan, A.Y.Y.; Charoenkwan, P.; Ng, I. .L.; Law, H.Y.; Ma, E.S.K.; Xu, X.M.; Wanapirak, C.; Sanguansermsri, T.; Liao, C.; Tan, J.A.M.A.; Chui, D.H.K.; Cantor, C.R.; Lo, Y.M.D. (2004) MS analysis of single-nucleotide differences in circulating nucleic acids: application to noninvasive prenatal diagnosis. Proceedings of the National Academy of Sciences of the United States of America, 101 (29). pp. 10762-10767. ISSN 0027-8424

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    Abstract

    The analysis of circulating nucleic acids has revealed applications in the noninvasive diagnosis, monitoring, and prognostication of many clinical conditions. Circulating fetal-specific sequences have been detected and constitute a fraction of the total DNA in maternal plasma. The diagnostic reliability of circulating DNA analysis depends on the fractional concentration of the targeted sequence, the analytical sensitivity, and the specificity. The robust discrimination of single-nucleotide differences between circulating DNA species is technically challenging and demands the adoption of highly sensitive and specific analytical systems. We have developed a method based on single-allele base extension reaction and MS, which allows for the reliable detection of fetal-specific alleles, including point mutations and single-nucleotide polymorphisms, in maternal plasma. The approach was applied to exclude the fetal inheritance of the four most common Southeast Asian beta-thalassemia mutations in at-risk pregnancies between weeks 7 and 21 of gestation. Fetal genotypes were correctly predicted in all cases studied. Fetal haplotype analysis based on a single-nucleotide polymorphism linked to the beta-globin locus, HBB, in maternal plasma also was achieved. Consequently, noninvasive prenatal diagnosis in a mother and father carrying identical beta-thalassemia mutations was accomplished. These advances will help in catalyzing the clinical applications of fetal nucleic acids in maternal plasma. This analytical approach also will have implications for many other applications of circulating nucleic acids in areas such as oncology and transplantation.

    Item Type: Article
    Creators:
    1. Ding, C.M.
    2. Chiu, R.W.K.
    3. Lau, T.K.
    4. Leung, T.N.
    5. Chan, L.C.
    6. Chan, A.Y.Y.
    7. Charoenkwan, P.
    8. Ng, I. .L.
    9. Law, H.Y.
    10. Ma, E.S.K.
    11. Xu, X.M.
    12. Wanapirak, C.
    13. Sanguansermsri, T.
    14. Liao, C.
    15. Tan, J.A.M.A.(Department of Molecular Medicine, Faculty of Medicine Building, University of Malaya, 50603 Kuala Lumpur, MALAYSIA)
    16. Chui, D.H.K.
    17. Cantor, C.R.
    18. Lo, Y.M.D.
    Journal or Publication Title: Proceedings of the National Academy of Sciences of the United States of America
    Additional Information: Department of Molecular Medicine, Faculty of Medicine Building, University of Malaya, 50603 Kuala Lumpur, MALAYSIA
    Uncontrolled Keywords: Molecular Medicine; Fetal haplotype
    Subjects: R Medicine
    Divisions: Faculty of Medicine
    Depositing User: Ms Haslinda Lahuddin
    Date Deposited: 08 Oct 2012 10:38
    Last Modified: 08 Oct 2012 10:38
    URI: http://eprints.um.edu.my/id/eprint/3723

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