PDbase: A database of Parkinson

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PDbase A database of Parkinsons
Disease-related genes and genetic variation using
substantia nigra ESTs

• Jin Ok Yang
• Korean BioInformation Center (KOBIC)
• E-mail joy_at_kribb.re.kr

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Abbreviation

• PD Parkinsons 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
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Pathology Diagnosis of PD

• Degeneration of Dopaminergic Neurons in
  Substantia Nigra
• Lewy body pathologic hallmark of PD,
  cytoplasmic inclusion body

Lewy 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 Parkinsons
  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
• 4080 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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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.
• PDs SN
• male caucasian 60 yrs of age, diagnosed with
  PD, died from a gun shot
• wound, negative for HIV 1/2, HBV and HCV.

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UniGene collection process

• Cell and Tissue Banking
• Parkinsons disease
• - PDs 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
UniGene Fl-length cDNA Database
cDNA Chip
Protein
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SN cDNA Libraries Summary
Source Library Name Library Type Reads UniGene 217 UniGene 217
Source Library Name Library Type Reads Gene Clusters
SN normal tissue SN normal tissue SN normal tissue SN normal tissue SN normal tissue SN normal tissue
Substantia Nigra B6NSN0 Full-length 2,056 600 619
B6NSN0n1 Full-length, Normalized 983 356 375
PD SN tissue PD SN tissue PD SN tissue PD SN tissue PD SN tissue PD SN tissue
Substantia Nigra B7PSN0 Full-length 2,053 738 750
B7PSN0n1 Full-length, Normalized 975 798 831
Number of clusters and genes in NCBI UniGene
build217 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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PD SN ESTs
Alternative splicing events (UniGene isoforms)
Differential expression (Audic algorithm)
Homologous genes (BLAST)
Normal SN ESTs
dbSNP
PD-related SNPs
Gene regulation
PDbase
Merged PD-related Gene information
Gene Ontology
Biological Pathways
Protein-protein Interaction
PD-related genes
PD-related SNPs
Gene Protein
dbSNP
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Web interface
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Gene Symbol 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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(No Transcript)
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Results_1 for the selected gene
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Results_2 for the selected gene
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• Partners
• FTH1
• MAP3K12
• GADD45A
• PTN
• MYOC
• SMAD9
• KNG1
• TAF10
• MPHOSPH6
• MPP6
• PUNC

FTL
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Conclusion

• PDbase
• Provides comprehensive information about
  Parkinsons Disease-related genes and genetic
  variation
• highlights to contain not only public resources,
  but also un-reported PD target genes using normal
  and PDs 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/