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Jin Ok Yang Korean BioInformation Center (KOBIC) E-mail: joy@kribb.re.kr

PD base : A database of Parkinson’s Disease-related genes and genetic variation using substantia nigra ESTs. Jin Ok Yang Korean BioInformation Center (KOBIC) E-mail: joy@kribb.re.kr. Abbreviation. PD: Parkinson’s Disease SN: Substantia Nigra. Parkinson’ Disease (PD). • PD

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Jin Ok Yang Korean BioInformation Center (KOBIC) E-mail: joy@kribb.re.kr

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  1. PDbase: A database of Parkinson’s Disease-related genes and genetic variation using substantia nigra ESTs Jin Ok Yang Korean BioInformation Center (KOBIC) E-mail: joy@kribb.re.kr

  2. Abbreviation • PD: Parkinson’s Disease • SN: Substantia Nigra

  3. Parkinson’ Disease (PD) • • PD • Neurodegenerative movement disorder • Late-onset neurological disorder, after the age of 50 • • Symptoms • : slowness of movement, rest tremor, rigidity, anxiety, • depression, disturbance in balance, autonomic disturbance • • Degeneration of dopaminergic (DA) neurons in Substantia Nigra (SN) • : loss of pigmented neurons in the pars compacta of the SN

  4. PD Normal PET scan Pathology & Diagnosis of PD • Degeneration of Dopaminergic Neurons in Substantia Nigra • Lewy body : pathologic hallmark of PD, cytoplasmic inclusion body Lewy Body

  5. Background • The substantia nigra (SN) is important resource to understand the mechanism of the PD causation • The needs for the resources to provide information of comprehensive PD-related genes and genetic variations • We present a consolidated PD database, called PDbase, to capture wide spectrum of molecular events

  6. PDbase database • PDbase • A comprehensive PD-related genes and genetic variation database • Contains 2,678 genes and 870,468 SNPs from 1) SN ESTs and 2) public disease-related databases • Provides biological function of the PD-related genes including alternative splicing events, SNPs located in gene structure, mitochondrial proteins, micro-RNA elements, biological pathways, and PPI networks Related work • MDPD (The Mutation Database for Parkinson’s Disease) • 202 genes extracted from 576 publications and manually examined by biomedical researchers based on population studies • It provides the PD-related genetic variation effects such as risk factor or ethnic group • PDGene • 40~80 PD genetic association studies • PD-related genes and risk factors from association studies

  7. PDbase construction: SN EST discovery and computational analysis

  8. Substantia Nigra (SN) ESTs collection • Global approaches • Useful in the analysis of complex biological phenomena, including certain human diseases. • Helpful to examine general gene expression • in the transcriptome. • ** Information of SN samples • normal SN tissue ; • male caucasian 81 yrs of age, died congestive heart failure, • negative for HIV 1/2, HBV and HCV. • PD’s SN ; • male caucasian 60 yrs of age, diagnosed with PD, died from a gun shot • wound, negative for HIV 1/2, HBV and HCV.

  9. UniGene collection process • Cell and Tissue Banking • Parkinson’s disease : • - PD’s SN Tissues • - Normal SN Tissues Human Cell & Tissue cDNA library (Normalized, Full-length) Picking & Gridding • High-diverse cDNA library • Full-length cDNA library • Normalized cDNA library Automatic DNA Extraction Workstation for Sequencing Reaction PCR • Large-scale cDNA sequencing • Automatic colony picking • Automatic plasmid DNA prep • Automatic reaction mixing Purification of Reaction Mixture Run on Auto-Sequencer • Base call, Editing, and Clustering • Phrep & Phred • CAP3 • Bioinformatics Group Data Editing & Assembly cDNA Chip UniGene & Fl-length cDNA Database Protein

  10. SN cDNA Libraries Summary *Number of clusters and genes in NCBI UniGene build#217 contributed by our EST sequences

  11. Alternative Splicing events We discovered SN ESTs from Full-length cDNA libraries based on oligo-capping methods

  12. Significant differences in gene expression

  13. PDbase system

  14. Disease PD’ SN ESTs Differential expression (Audic algorithm) Alternative splicing events (UniGeneisoforms) Homologous genes (BLAST) Normal SN ESTs Uniprot Refseq mitoDat dbSNP Mapping (BLAST) PD-related SNPs UMLS GAD HGNC HGMD OMIM Gene regulation PDbase Merged PD-related Gene information Gene Ontology Biological Pathways Protein-protein Interaction PD-related genes PD-related SNPs Gene & Protein dbSNP

  15. Web interface 1 2

  16. Query Results • SN EST statistics • Gene information • Genetic variation information • Gene regulation • Gene Ontology (GO) • Biological pathways: BioCarta and KEGG • Protein-protein interaction network

  17. Results_1 for the selected gene

  18. Results_2 for the selected gene

  19. *Partners • FTH1 • MAP3K12 • GADD45A • PTN • MYOC • SMAD9 • KNG1 • TAF10 • MPHOSPH6 • MPP6 • PUNC FTL

  20. Conclusion • PDbase • Provides comprehensive information about Parkinson’s Disease-related genes and genetic variation • highlights to contain not only public resources, but also un-reported PD target genes using normal and PD’s SN ESTs • Helpful in analysis of complex biological phenomena including human brain diseases because of including several genes, genetic variations, expression, and network • available at http://bioportal.kobic.re.kr/PDbase/

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