Analysis of non-synonymous-coding variants of Parkinson's disease-related pathogenic and susceptibility genes in East Asian populations.

To evaluate the contribution of non-synonymous-coding variants of known familial and genome-wide association studies (GWAS)-linked genes for Parkinson's disease (PD) to PD risk in the East Asian population, we sequenced all the coding exons of 39 PD-related disease genes and evaluated the accumulation of rare non-synonymous-coding variants in 375 early-onset PD cases and 399 controls. We also genotyped 782 non-synonymous-coding variants of these genes in 710 late-onset PD cases and 9046 population controls. Significant enrichment of LRRK2 variants was observed in both early- and late-onset PD (odds ratio = 1.58; 95% confidence interval = 1.29-1.93; P = 8.05 × 10(-6)). Moderate enrichment was also observed in FGF20, MCCC1, GBA and ITGA8. Half of the rare variants anticipated to cause loss of function of these genes were present in healthy controls. Overall, non-synonymous-coding variants of known familial and GWAS-linked genes appear to make a limited contribution to PD risk, suggesting that clinical sequencing of these genes will provide limited information for risk prediction and molecular diagnosis.

Rapid carrier screening for beta-thalassemia by single-step allele-specific PCR and detection.

OBJECTIVES: This study aimed to evaluate a rapid molecular carrier screening strategy for beta-thalassemia. DESIGN AND METHODS: Allele-specific PCR was combined with amplicon detection by dissociation curve analysis of SYBR Green I fluorescence in a single step. RESULTS: The presence of a particular mutation results in the amplification of a mutation-specific product and the dissociation temperature of each amplicon was highly reproducible. CONCLUSIONS: Homogeneous allele-specific PCR amplification and detection of multiple beta-globin mutations can serve as a rapid and inexpensive carrier screening tool.