Development of new SNP typing technologies for searching disease-associated genes.

为了建立可靠的核苷酸序列多态分型技术，我们首先建立了一种新的人类白细胞抗原-DRB1基因分型系统，该基因具有最高的多态程度，与许多疾病有显著的相关性。带有腔室的玻璃阵列使打字过程与微量滴定板的打字程序相似。接下来，我们开发了一种用于疾病相关SNPs分型的微毛细管阵列。在每个毛细管中都发现了许多不同的寡核苷酸探针，每个探针在通过毛细管后提供了一个特定的杂交信号。因此，该系统可能适用于多重和自动化的SNP分型。此外，我们还可以建立一种新的SNP分型体系，将PCR-SSP与荧光相关光谱相结合。该系统已用于常规SNP分型，是一种大规模、高性价比的SNP分型系统。此外，我们还发现了几个与风湿病相关的SNPs，包括FCGR2B、FCGR3A和LIR1基因。

In order to establish reliable technologies for typing nucleotide sequence polymorphisms, we first developed a new typing system for the HLA-DRB1 gene, which shows a highest degree of polymorphism and significant associations with many diseases. A glass array with a chamber made the typing procedure similar to that for microtiter plates. Next we developed a micro-capillary array for the typing of disease-associated SNPs. Many different oligonucleotide probes were spotted in each capillary, and each probe provided a specific hybridization signal after washing through a capillary. Thus this system may be suitable for multiplex and automated SNP typing. In addition, we could establish a new SNP typing system in the combination of PCR-SSP with the fluorescence correlation spectroscopy. The system has been introduced to routine SNP typing and proved to be a large-scale and cost-effective system. Furthermore, we have identified several rheumatic disease-associated SNPs including those of FCGR2B, FCGR3A and LIR1 genes.