title: Identification of genes related to Parkinson's disease using expressed sequence tags.
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.
authors.affiliation: Laboratory of Human Genomics, Genome Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) Daejeon, Korea.
authors.forename: Jeong-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Kyu-Hwa
authors.initials: KH
authors.lastname: Lee
authors.forename: Yeo-Jin
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Oh
authors.forename: So-Young
authors.initials: SY
authors.lastname: Jeong
authors.forename: In-Sung
authors.initials: IS
authors.lastname: Song
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Lee
authors.forename: Nam-Soon
authors.initials: NS
authors.lastname: Kim
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D016923:Cell Death; D002864:Chromogranins; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D020224:Expressed Sequence Tags / Q000737:chemistry*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism; D015723:Gene Library; D020022:Genetic Predisposition to Disease; D005821:Genetic Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009498:Neurotoxins / Q000009:adverse effects; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002864:Chromogranins; D003598:Cytoskeletal Proteins; C482331:DNMBP protein, human; C485840:DOCK3 protein, human; D020662:Guanine Nucleotide Exchange Factors; C499048:MBP protein, human; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; C506895:SPP1 protein, human; D014157:Transcription Factors; D053495:Osteopontin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs