title: Proteomic analysis of maternal serum in down syndrome: identification of novel protein biomarkers.
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.
authors: Department of Pediatrics, Oregon Health and Science University, Portland, Oregon 97239, USA. nagallas@ohsu.edu
authors: Srinivasa R
authors: SR
authors: Nagalla
authors: Jacob A
authors: JA
authors: Canick
authors: Thomas
authors: T
authors: Jacob
authors: Kimberly A
authors: KA
authors: Schneider
authors: Ashok P
authors: AP
authors: Reddy
authors: Archana
authors: A
authors: Thomas
authors: Surendra
authors: S
authors: Dasari
authors: Xinfang
authors: X
authors: Lu
authors: Jodi A
authors: JA
authors: Lapidus
authors: Geralyn M
authors: GM
authors: Lambert-Messerlian
authors: Michael G
authors: MG
authors: Gravett
authors: Charles T
authors: CT
authors: Roberts
authors: David
authors: D
authors: Luthy
authors: Fergal D
authors: FD
authors: Malone
authors: Mary E
authors: ME
authors: D'Alton
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D004314:Down Syndrome / Q000097:blood* / Q000175:diagnosis*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D010455:Peptides / Q000032:analysis; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D006023:Glycoproteins; D010455:Peptides