Proteomic analysis of maternal serum in down syndrome: Identification of novel protein biomarkers

Srinivasa R. Nagalla, Jacob A. Canick, Thomas Jacob, Kimberly A. Schneider, Ashok P. Reddy, Archana Thomas, Surendra Dasari, Xinfang Lu, Jodi A. Lapidus, Geralyn M. Lambert-Messerlian, Michael G. Gravett, Charles T. Roberts, David Luthy, Fergal D. Malone, Mary E. D'Alton

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


Down syndrome (DS) is the most prevalent chromosomal disorder, accounting for significant morbidity and mortality. Definitive diagnosis requires invasive amniocentesis, and current maternal serum-based testing requires a false-positive rate of about 5% to detect 85% of affected pregnancies. We have performed a comprehensive proteomic analysis to identify potential serum biomarkers to detect DS. First- and second-trimester maternal serum samples of DS and gestational age-matched controls were analyzed using multiple, complementary proteomic approaches, including fluorescence 2-dimensional gel electrophoresis (2D-DIGE), 2-dimensional liquid chromatography-chromatofocusing (2D-CF), multidimensional protein identification technology (MudPIT; LC/LC-MS/MS), and MALDI-TOF-MS peptide profiling. In total, 28 and 26 proteins were differentially present in first- and second-trimester samples, respectively. Of these, 19 were specific for the first trimester and 16 for the second trimester, and 10 were differentially present in both trimesters. Analysis of MALDI-TOF-MS peptide profiles with pattern-recognition software also discriminated between DS and controls in both trimesters, with an average recognition capability approaching 96%. A majority of the biomarkers identified are serum glycoproteins that may play a role in cellular differentiation and growth of fetus. Further characterization and quantification of these markers in a larger cohort of subjects may provide the basis for new tests for improved DS screening.

Original languageEnglish (US)
Pages (from-to)1245-1257
Number of pages13
JournalJournal of Proteome Research
Issue number4
StatePublished - Apr 2007


  • Aneuploidy
  • Chrom
  • Pregnancy
  • Prenatal screening

ASJC Scopus subject areas

  • Biochemistry
  • General Chemistry


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