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Analysis of whole genome biomarker expression in blood and brain

Authors

  • Brandi Rollins,

    1. Department of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine, California
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    • Brandi Rollins and Maureen V. Martin contributed equally to this work.

  • Maureen V. Martin,

    1. Department of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine, California
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    • How to Cite this Article: Rollins B, Martin MV, Morgan L, Vawter MP. 2010. Analysis of Whole Genome Biomarker Expression in Blood and Brain. Am J Med Genet Part B 153B: 919–936.

  • Ling Morgan,

    1. Department of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine, California
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  • Marquis P. Vawter

    Corresponding author
    1. Department of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine, California
    • Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, School of Medicine, University of California, 837 Health Science Drive, Gillespie Neuroscience Facility Room 2119, Irvine, CA 92697-4260.
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  • No authors on this paper have a conflict of interest to declare.

Abstract

The consistency of peripheral gene expression data and the overlap with brain expression has not been evaluated in biomarker discovery, nor has it been reported in multiple tissues from the same subjects on a genome wide transcript level. The effects of processing whole blood, transformation, and passaged cell lines on gene expression profiling was studied in healthy subjects using Affymetrix arrays. Ficoll extracted peripheral blood mononuclear cells (PBMCs), Epstein–Barr virus (EBV) transformed lymphocytes, passaged lymphoblastic cell lines (LCLs), and whole blood from Tempus tubes were compared. There were 6,813 transcripts differentially expressed between different methods of blood preparation. Principal component analysis resolved two partitions involving pre- and post-transformation EBV effects. Combining results from Affymetrix arrays, postmortem subjects' brain and PBMC profiles showed co-expression levels of summarized transcripts for 4,103 of 17,859 (22.9%) RefSeq transcripts. In a control experiment, rat hemi-brain and blood showed similar expression levels for 19% of RefSeq transcripts. After filtering transcripts that were not significantly different in abundance between human cerebellum and PBMCs from the Affymetrix exon array the correlation in mean transcript abundance was high as expected (r = 0.98). Differences in the alternative splicing index in brain and blood were found for about 90% of all transcripts examined. This study demonstrates over 4,100 brain transcripts co-expressed in blood samples can be further examined by in vitro and in vivo experimental studies of blood and cell lines from patients with psychiatric disorders. © 2010 Wiley-Liss, Inc.

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