| Budget Amount *help |
¥36,000,000 (Direct Cost: ¥36,000,000)
Fiscal Year 2004: ¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2003: ¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2002: ¥12,000,000 (Direct Cost: ¥12,000,000)
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| Research Abstract |
Parkinson's disease (PD) is a complex disorder with multiple genetic and environmental factors influencing disease risk. Although several causal genes for Mendelian inherited PD have recently been identified, strong genetic factors that influence idiopathic PD have not yet been identified. To identify susceptibility genes for idiopathic PD, we performed a genome-wide association study using 27,000 microsatellite markers arranged at intervals of 100kb throughout the genome. For the initial screening, we compared the pattern of the PCR products of pooled DNA from 124 patients with PD and 124 controls. We analyzed the 27,000 markers and found associations (p<0.05) in 7.8% of the markers. Then, we have performed systematic and comprehensive 2nd and 3rd screenings on all of these candidate markers using other sets of pooled DNA to exclude false positive associations. and expect that approximately 30 markers will show significant associations throughout all three screenings.
Secondly, we have done case-control analysis by using SNPs in multiple candidate genes. We selected candidate genes from the viewpoints of familial PD, dopaminergic neurons, trophic factors, oxidative stress, mitochondria, apoptosis, ubiquitin-proteasome, autophagy, etc. For initial screening, we genotyped 190 patients and 190 controls by Invader method. Of 267 SNPs in 122 candidate genes, 22 SNPs in 16 genes showed p<0.05. We are now confirming these associations by increasing the number of samples to nearly 900 for patients and 900 for controls.
SNPs in linkage disequilibrium with these markers may be associated with the pathogenesis of PD.
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