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DNA Research Advance Access originally published online on January 8, 2007
DNA Research 2006 13(6):275-286; doi:10.1093/dnares/dsl016
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© The Author 2006. Kazusa DNA Research Institute
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Identification of Genes Related to Parkinson's Disease Using Expressed Sequence Tags

Jeong-Min Kim1, Kyu-Hwa Lee1, Yeo-Jin Jeon1, Jung-Hwa Oh1, So-Young Jeong1, In-Sung Song1, Jin-Man Kim2, Dong-Seok Lee3 and Nam-Soon Kim1,*

1 Laboratory of Human Genomics, Genome Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) Daejeon, Korea
2 Department of Pathology, College of Medicine, Chungnam National University Daejeon, Korea
3 College of animal resource sciences, Kangwon National University Chunchon, Korea

In a search for novel target genes related to Parkinson's disease (PD), two full-length cDNA libraries were constructed from a human normal substantia nigra (SN) and a PD patient's SN. An analysis of the gene expression profiles between them was done using the expressed sequence tags (ESTs) frequency. Data for the differently expressed genes were verified by quantitative real-time RT–PCR, immunohistochemical analysis and a cell death assay. Among the 76 genes identified with a significant difference (P > 0.9), 21 upregulated genes and 13 downregulated genes were confirmed to be differentially expressed in human PD tissues and/or in an MPTP-treated mice model by quantitative real-time RT–PCR. Among those genes, an immunohistochemical analysis using an MPTP mice model for alpha-tubulin including TUBA3 and TUBA6 showed that the protein levels are downregulated, as well as the RNA levels. In addition, MBP, PBP and GNAS were confirmed to accelerate cell death activity, whereas SPP1 and TUBA3 to retard this process. Using an analysis of ESTs frequency, it was possible to identify a large number of genes related to human PD. These new genes, MBP, PBP, GNAS, SPP1 and TUBA3 in particular, represent potential biomarkers for PD and could serve as useful targets for elucidating the molecular mechanisms associated with PD.

Key words: parkinson's disease; expressed sequence tags; gene expression profiling; immunohistochemistry; cell death

*To whom correspondence should be addressed. Tel. +82-42-879-8112, Fax. +82-42-879-8119. E-mail: nskim37{at}kribb.re.kr

Communicated by Shoji Tsuji Sequence data from this article have been deposited with the GenBank Data Libraries under Accession Nos DT214917 [GenBank] –DT221046 [GenBank] .


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