Proteomic analysis of maternal serum in down syndrome: identification of novel protein biomarkers |
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Authors: | 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 |
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Institution: | Department of Pediatrics, Oregon Health and Science University, Portland, Oregon 97239, USA. nagallas@ohsu.edu |
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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. |
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