Quantitative proteomic analysis of amniocytes reveals potentially dysregulated molecular networks in Down syndrome

Clinical Proteomics

George S Karagiannis¹  Shawn Dason³  Eduardo Martínez-Morillo²  Apostolos Dimitromanolakis²  Chan-Kyung J Cho³  Andrei P Drabovich²  Eleftherios P Diamandis⁴ 

[1] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, CanadaSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada;Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, CanadaSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, CanadaSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada

关键词: Down syndrome;    Trisomy 21;    Amniocyte;    Amniotic fluid cells;    Quantitative proteomics;   

DOI  :  10.1186/1559-0275-10-2

来源: Humana Press Inc

【 摘 要 】

Abstract

Background

Down syndrome (DS), caused by an extra copy of chromosome 21, affects 1 in 750 live births and is characterized by cognitive impairment and a constellation of congenital defects. Currently, little is known about the molecular pathogenesis and no direct genotype-phenotype relationship has yet been confirmed. Since DS amniocytes are expected to have a distinct biological behaviour compared to normal amniocytes, we hypothesize that relative quantification of proteins produced from trisomy and euploid (chromosomally normal) amniocytes will reveal dysregulated molecular pathways.

Results

Chromosomally normal- and Trisomy 21-amniocytes were quantitatively analyzed by using Stable Isotope Labeling of Amino acids in Cell culture and tandem mass spectrometry. A total of 4919 unique proteins were identified from the supernatant and cell lysate proteome. More specifically, 4548 unique proteins were identified from the lysate, and 91% of these proteins were quantified based on MS/MS spectra ratios of peptides containing isotope-labeled amino acids. A total of 904 proteins showed significant differential expression and were involved in 25 molecular pathways, each containing a minimum of 16 proteins. Sixty of these proteins consistently showed aberrant expression from trisomy 21 affected amniocytes, indicating their potential role in DS pathogenesis. Nine proteins were analyzed with a multiplex selected reaction monitoring assay in an independent set of Trisomy 21-amniocyte samples and two of them (SOD1 and NES) showed a consistent differential expression.

Conclusions

The most extensive proteome of amniocytes and amniotic fluid has been generated and differentially expressed proteins from amniocytes with Trisomy 21 revealed molecular pathways that seem to be most significantly affected by the presence of an extra copy of chromosome 21.

【 授权许可】

Unknown