• Zhiming Li, Qing Lin, Wenqing Huang, and Chi-Meng Tzeng.
• From the School of Pharmaceutical Sciences, Xiamen University (ZL, QL, WH, C-MT); and Department of Neurology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China (QL).
• Medicine (Baltimore). 2015 May 1; 94 (20): e836e836.

AbstractDeciphering of genetic variants plays a critical role in research and clinic of genetic disorders, such as the well known neurodegenerative disease Parkinson disease (PD). To combine pool of targeted genes and next-generation sequencing (NGS), investigators could obtain high efficient but low-cost sequencing data of interested genes. Aim to discover genetic variants that might contribute to PD, we selected 48 candidate genes involved in different pathways and conducted a pilot study to screen nonsynonymous SNPs (nsSNPs) in 4 pooled samples from 237 sporadic Chinese PD patients. Using our custom-designed NimbleGen array and Illumina HiSeq2000, a total of 4 novel nsSNPs (c. 352G>T in STK39, c. 823G>T in DGKQ, c. 36T>A in DLA-DRB5, and c. 1981G>T in GRN) were discovered but not validated by Sanger sequencing. Additionally, we also selected 6 annotated nsSNPs without report in previous PD studies and validated by Sanger sequencing. However, genotyping analysis of 6 validated nsSNPs in 50 PD patients and 50 controls showed no significant differences in cases compared with controls. These data represent the first documentation and validation of these mutations in PD using target gene capture sequencing. Additional replication studies in other populations and functional research are merited to better evaluate precapture multiplex protocol and validate the role of the 6 nsSNPs in PD risk.

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