Large Scale Single Nucleotide Polymorphism Study of PD Susceptibility

摘要

Although genetic contributions of Parkinson's disease (PD) have gained support from the recent identification of eight genetic loci in the familial PD, the results of intensive investigations of polymorphisms in dozens of genes related to sporadic, late onset, typical PD have not shown consistent results. Recent rapid progress in the investigation of single nucleotide polymorphisms (SNPs) has provided a new tool for this area of research. Millions of SNPs have been identified and compiled in several publicly accessible databases. A highly multiplexed genotyping technology called 'Molecular Inversion Probe Assay' (MIPA) has recently been developed. This technique is capable of genotyping over 2,000 SNPs in a single tube and is currently the least expensive platform for genotyping of SNPs with high call rate and high accuracy. Another major finding in recent genomic studies is that haplotype linkage disequilibrium is composed of blocks of sequence with an average size of 7.8 kb and could be used in associated studies. In this proposal, the authors plan to perform a large-scale association study by using the high throughput MIPA in PD to do the following: (1) investigate the association between classical, sporadic PD and 2,386 SNPs in 23 genes implicated in the pathogenesis of PD; and (2) construct haplotypes based on the SNP genotyping results to identify haplotypes associated with PD. This proposal is the first large-scale SNP association study in PD. The results of this study may lead to a better understanding of the pathogenesis of the disease and possible new therapeutic approaches. In addition, experiences derived from this study may be applied to other complex disorders for the identification of susceptibility genes, as well as in genome-wide SNP association studies.