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DNA Research Advance Access published online on January 8, 2007
DNA Research, doi:10.1093/dnares/dsl016
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© The Author 2006. Kazusa DNA Research Institute.
Received April 26, 2006
Revised November 20, 2006

Full Papers

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

Jeong-Min Kim 1, Kyu-Hwa Lee 1, Yeo-Jin Jeon 1, Jung-Hwa Oh 1, So-Young Jeong 1, In-Sung Song 1, Jin-Man Kim 2, Dong-Seok Lee 3, and Nam-Soon Kim 1 *

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

* To whom correspondence should be addressed.
Nam-Soon Kim, E-mail: nskim37{at}kribb.re.kr


  Abstract

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.

Keywords: parkinson's disease; expressed sequence tags; gene expression profiling; immunohistochemistry; cell death.

Communicated by Shoji Tsuji

Sequence data from this article have been deposited with the GenBank Data Libraries under Accession Nos DT214917- DT221046.


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