Feasibility study for a microchip-based approach for noninvasive prenatal diagnosis of genetic diseases

L. Cremonesi, S. Galbiati, B. Foglieni, M. Smid, D. Gambini, A. Ferrari, E. Viora, M. Campogrande, M. Pagliano, M. Travi, A. Piga, G. Restagno, M. Ferrari

Research output: Contribution to journalArticle

Abstract

Fetal DNA in maternal plasma may represent a source of genetic material for prenatal noninvasive diagnosis of genetic diseases. We evaluated a cohort of physiological pregnancies to determine if fetal DNA can be retrieved at any gestational week in sufficient quantity to be analyzed with advanced mutation detection technologies. We performed fetal DNA quantification by real-time polymerase chain reaction (PCR) on the SRY gene in 356 women sampled from 6 to 40 gestational weeks. Fetal DNA was retrieved at any week. All female fetuses were correctly identified. In 5 of 188 (2.6%) male-bearing pregnancies, no amplification was obtained. For noninvasive testing, complete clearance of fetal DNA after delivery is mandatory. Long-term persistence was not detected in women with previous sons or abortions. These findings confirm that maternal plasma may represent the optimal source of fetal genetic material. For noninvasive diagnosis of genetic diseases, we evaluated microchip technology. The detection limit for a minority allele determined by diluting a mutated DNA into a wild-type plasma sample was 5 genome equivalents, indicating that the test might be applied to the identification of paternally inherited fetal alleles in maternal plasma. The addition of peptide nucleic acids (PNAs) to either the PCR reaction or the chip hybridization mixture allowed approximately 50% inhibition of wild-type allele signals.

Original languageEnglish
Pages (from-to)105-112
Number of pages8
JournalAnnals of the New York Academy of Sciences
Volume1022
DOIs
Publication statusPublished - 2004

Keywords

  • Circulating DNA
  • Fetal DNA
  • Maternal plasma
  • Noninvasive prenatal diagnosis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Cremonesi, L., Galbiati, S., Foglieni, B., Smid, M., Gambini, D., Ferrari, A., Viora, E., Campogrande, M., Pagliano, M., Travi, M., Piga, A., Restagno, G., & Ferrari, M. (2004). Feasibility study for a microchip-based approach for noninvasive prenatal diagnosis of genetic diseases. Annals of the New York Academy of Sciences, 1022, 105-112. https://doi.org/10.1196/annals.1318.017