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.
Article first published online: 2 FEB 2010
Copyright © 2010 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 153B, Issue 4, pages 919–936, June 2010
How to Cite
Rollins, B., Martin, M. V., Morgan, L. and Vawter, M. P. (2010), Analysis of whole genome biomarker expression in blood and brain. Am. J. Med. Genet., 153B: 919–936. doi: 10.1002/ajmg.b.31062
No authors on this paper have a conflict of interest to declare.
- Issue published online: 17 MAY 2010
- Article first published online: 2 FEB 2010
- Manuscript Accepted: 14 DEC 2009
- Manuscript Received: 21 MAY 2009
- NIMH Conte Center. Grant Number: P50 MH60398
- Pritzker Family Philanthropic Fund
- Public Health Service Research Grant. Grant Number: M01 RR00827
- National Center for Research Resource, Biomarker Research Grant. Grant Number: MH 024370
- National Institute of Mental Health
- William Lion Penzner Foundation (Department of Psychiatry)
- gene expression;
- whole genome
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.