Elucidation of molecular mechanisms of Parkinson disease based on comprehensive nucleotide sequence analysis of glucocerebrosidase gene.

点击翻译按钮获取中文摘要

This study aimed to elucidate susceptibility genes for sporadic Parkinson disease. Comprehensive resequencing analysis of GBA (glucocerebrosidase gene) has been conducted using 534 Japanese cases of sporadic Parkinson disease and 544 Japanese healthy controls. We found that the frequency of cases of Parkinson disease with heterozygous variants of GBA was 9.4%, which was significantly more frequent than that of controls (0.37%) with the odds ratio of 28.0 (95% CI : 4.3-238.3, p=6.9X10^<-14>). We furthermore conducted international collaboration to explore whether heterozygous variants of GBA confer such a strong risk for Parkinson disease irrespective of ethnicity. We confirmed that heterozygous variants of GBA confers a strong risk for Parkinson disease irrespective of ethnicity. These results strongly indicate that comprehensive resequencing analysis is necessary to identify rare variants. To enable comprehensive resequencing of large data sets, we applied next generation sequencers to analyze pooled DNA. We demonstrated that we can sensitively and accurately determine the allele frequencies of variants using pooled genomic DNA consisting of 6 samples.