Document Detail

Amniotic fluid proteome analysis from Down syndrome pregnancies for biomarker discovery.
MedLine Citation:
PMID:  20459121     Owner:  NLM     Status:  MEDLINE    
Down syndrome (DS) is an anomaly caused by an extra chromosome 21, and it affects 1 in 750 live births. Phenotypes include cognitive impairment, congenital defects, and increased risk for several diseases such as Alzheimer's disease and leukemia. Current DS-screening tests subject many women to invasive procedures for accurate diagnosis due to insufficient specificity. Since amniotic fluid (AF) surrounds the developing fetus, understanding the changes in AF composition in the presence of DS may provide insights into genotype-phenotype associations, and aid in discovery of novel biomarkers for better screening. On the basis of our previous study, in which we reported an extensive proteome of AF, we performed two-dimensional liquid chromatography followed by MS/MS to analyze triplicates of pooled AF of chromosomally normal and DS-affected pregnancies (10 samples per pool). A total of 542 proteins were identified from the two sets of triplicate analyses by the LTQ-Orbitrap mass spectrometer and data were compared semiquantitatively by spectral counting. Candidate biomarkers were selected based on the spectral count differences between the two conditions after normalization. Comparison between the two groups revealed 60 candidates that showed greater than 2-fold increase or decrease in concentration in the presence of DS. Among these candidates, amyloid precursor protein and tenascin-C were verified by ELISA, and both showed a 2-fold increase, on average, in DS-AF samples compared to controls. All proteins that showed significant differences between the two conditions were bioinformatically analyzed to preliminarily understand their biological implications in DS.
Chan-Kyung J Cho; Christopher R Smith; Eleftherios P Diamandis
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of proteome research     Volume:  9     ISSN:  1535-3907     ISO Abbreviation:  J. Proteome Res.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-02     Completed Date:  2010-10-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101128775     Medline TA:  J Proteome Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3574-82     Citation Subset:  IM    
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
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MeSH Terms
Amniotic Fluid / chemistry*
Amyloid beta-Protein Precursor / analysis,  metabolism
Biological Markers / analysis*
Cluster Analysis
Down Syndrome / metabolism*
Electrophoresis, Gel, Two-Dimensional
Enzyme-Linked Immunosorbent Assay
Gestational Age
Middle Aged
Prenatal Diagnosis
Proteome* / analysis,  metabolism
Reproducibility of Results
Signal Transduction
Tandem Mass Spectrometry
Tenascin / analysis,  metabolism
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/Amyloid beta-Protein Precursor; 0/Biological Markers; 0/Proteome; 0/Tenascin

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