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 journalArticle

83 Citations (Scopus)

Abstract

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
Volume6
Issue number4
DOIs
StatePublished - Apr 2007
Externally publishedYes

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Biomarkers
Down Syndrome
Proteomics
Mothers
Second Pregnancy Trimester
First Pregnancy Trimester
Peptides
Liquid chromatography
Electrophoresis
Serum
Pattern recognition
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Glycoproteins
Screening
Proteins
Gels
Fluorescence
Two-Dimensional Difference Gel Electrophoresis
Chromosome Disorders
Testing

Keywords

  • Aneuploidy
  • Chrom
  • Pregnancy
  • Prenatal screening

ASJC Scopus subject areas

  • Genetics
  • Biotechnology
  • Biochemistry

Cite this

Nagalla, S. R., Canick, J. A., Jacob, T., Schneider, K. A., Reddy, A. P., Thomas, A., ... D'Alton, M. E. (2007). Proteomic analysis of maternal serum in down syndrome: Identification of novel protein biomarkers. Journal of Proteome Research, 6(4), 1245-1257. https://doi.org/10.1021/pr060539h

Proteomic analysis of maternal serum in down syndrome : Identification of novel protein biomarkers. / Nagalla, Srinivasa R.; Canick, Jacob A.; Jacob, Thomas; Schneider, Kimberly A.; Reddy, Ashok P.; Thomas, Archana; Dasari, Surendra; Lu, Xinfang; Lapidus, Jodi A.; Lambert-Messerlian, Geralyn M.; Gravett, Michael G.; Roberts, Charles T.; Luthy, David; Malone, Fergal D.; D'Alton, Mary E.

In: Journal of Proteome Research, Vol. 6, No. 4, 04.2007, p. 1245-1257.

Research output: Contribution to journalArticle

Nagalla, SR, Canick, JA, Jacob, T, Schneider, KA, Reddy, AP, Thomas, A, Dasari, S, Lu, X, Lapidus, JA, Lambert-Messerlian, GM, Gravett, MG, Roberts, CT, Luthy, D, Malone, FD & D'Alton, ME 2007, 'Proteomic analysis of maternal serum in down syndrome: Identification of novel protein biomarkers', Journal of Proteome Research, vol. 6, no. 4, pp. 1245-1257. https://doi.org/10.1021/pr060539h
Nagalla, Srinivasa R. ; Canick, Jacob A. ; Jacob, Thomas ; Schneider, Kimberly A. ; Reddy, Ashok P. ; Thomas, Archana ; Dasari, Surendra ; Lu, Xinfang ; Lapidus, Jodi A. ; Lambert-Messerlian, Geralyn M. ; Gravett, Michael G. ; Roberts, Charles T. ; Luthy, David ; Malone, Fergal D. ; D'Alton, Mary E. / Proteomic analysis of maternal serum in down syndrome : Identification of novel protein biomarkers. In: Journal of Proteome Research. 2007 ; Vol. 6, No. 4. pp. 1245-1257.
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AU - Schneider, Kimberly A.

AU - Reddy, Ashok P.

AU - Thomas, Archana

AU - Dasari, Surendra

AU - Lu, Xinfang

AU - Lapidus, Jodi A.

AU - Lambert-Messerlian, Geralyn M.

AU - Gravett, Michael G.

AU - Roberts, Charles T.

AU - Luthy, David

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