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Transcript of PDbase : A database of Parkinson’s Disease-related genes and genetic variation using substantia...
![Page 1: PDbase : A database of Parkinson’s Disease-related genes and genetic variation using substantia nigra ESTs Jin Ok Yang Korean BioInformation Center (KOBIC)](https://reader035.fdocuments.us/reader035/viewer/2022062409/56649de85503460f94ae2237/html5/thumbnails/1.jpg)
PDbase: A database of Parkinson’s Disease-related
genes and genetic variation using substantia nigra ESTs
Jin Ok YangKorean BioInformation Center (KOBIC)
E-mail: [email protected]
![Page 2: PDbase : A database of Parkinson’s Disease-related genes and genetic variation using substantia nigra ESTs Jin Ok Yang Korean BioInformation Center (KOBIC)](https://reader035.fdocuments.us/reader035/viewer/2022062409/56649de85503460f94ae2237/html5/thumbnails/2.jpg)
Abbreviation
• PD: Parkinson’s Disease• SN: Substantia Nigra
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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
![Page 4: PDbase : A database of Parkinson’s Disease-related genes and genetic variation using substantia nigra ESTs Jin Ok Yang Korean BioInformation Center (KOBIC)](https://reader035.fdocuments.us/reader035/viewer/2022062409/56649de85503460f94ae2237/html5/thumbnails/4.jpg)
Pathology & Diagnosis of PD
Degeneration of Dopaminergic Neurons in Substantia Nigra Lewy body : pathologic hallmark of PD, cytoplasmic inclusion body
PET scan
Normal PDLewy Body
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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
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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
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PDbase construction:SN EST discovery and
computational analysis
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** 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.
• Global approaches Useful in the analysis of complex biological phenomena, including certain human diseases. Helpful to examine general gene expression
in the transcriptome.
Substantia Nigra (SN) ESTs collection
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• Cell and Tissue Banking
Parkinson’s disease :
- PD’s SN Tissues - Normal SN Tissues
• High-diverse cDNA library
Full-length cDNA library Normalized cDNA library
• Large-scale cDNA sequencing
Automatic colony picking Automatic plasmid DNA prep Automatic reaction mixing
• Base call, Editing, and Clustering
Phrep & Phred CAP3 Bioinformatics Group
UniGene collection processUniGene collection processUniGene collection processUniGene collection process
Human Cell & TissueHuman Cell & Tissue
cDNA library(Normalized, Full-length)
cDNA library(Normalized, Full-length)
Picking & GriddingPicking & Gridding
Automatic DNA Extraction
Automatic DNA Extraction
Workstation for Sequencing Reaction
Workstation for Sequencing Reaction
PCRPCR
Purification ofReaction Mixture
Purification ofReaction Mixture
Run on Auto-SequencerRun on Auto-Sequencer
Data Editing & AssemblyData Editing & Assembly
UniGene & Fl-lengthcDNA Database
UniGene & Fl-lengthcDNA DatabasecDNA ChipcDNA Chip
cDNA ChipcDNA ChipProteinProtein
ProteinProtein
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SourceLibrary Name
Library Type
ReadsUniGene #217*
Gene Clusters
SN normal tissue
Substantia Nigra B6NSN0 Full-length 2,056 600 619
B6NSN0n1 Full-length, Normalized
983 356 375
PD’ SN tissue
Substantia Nigra B7PSN0 Full-length 2,053 738 750
B7PSN0n1 Full-length, Normalized
975 798 831
SN cDNA Libraries Summary
*Number of clusters and genes in NCBI UniGene build#217 contributed by our EST sequences
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Alternative Splicing events
AS events Number of Genes associated with AS event
Alternative starts 119
Alternative ends 61
Retained intron 64
Cassette exon 45
Double cassette exon
9
Alternative 3’ exon 32
Alternative 5’ exon 19
We discovered SN ESTs from Full-length cDNA libraries based
on oligo-capping methods
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Significant differences in gene expression
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PDbase system
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PDbaseMerged PD-related Gene information
Alternative splicing events
(UniGene isoforms)
Gene regulation
Gene Ontology
Biological Pathways
Protein-protein Interaction
Normal SN ESTs
PD’ SN ESTs
Homologous genes(BLAST)
Differential
expression
(Audic algorithm
)
PD-related genes
dbSNP
PD-related SNPs
mitoDat
HGNC
Refseq
Uniprot
Mapping(BLAST)
HGMD
GAD
OMIM
UMLS
DiseaseGene & Protein
dbSNPPD-related
SNPs
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Web interface
1
2
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# GeneSymbol
Description More Information
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Query Results
– SN EST statistics– Gene information– Genetic variation information– Gene regulation– Gene Ontology (GO)– Biological pathways: BioCarta and KEGG– Protein-protein interaction network
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Results_1 for the selected gene
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Results_2 for the selected gene
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FTL
*Partners FTH1 MAP3K12 GADD45A PTN MYOC SMAD9 KNG1 TAF10 MPHOSPH6 MPP6 PUNC
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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/