Variations in immune response genes and their associations with multifactorial immune disorders
Variations in immune response genes and their associations with multifactorial immune disorders
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DOI：
10.1034/j.1600-065x.2002.19013.x
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发表时间：
2002-12
影响因子：
8.7
通讯作者：
N. Tsuchiya;J. Ohashi;K. Tokunaga
中科院分区：
文献类型：
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作者：
N. Tsuchiya;J. Ohashi;K. Tokunaga
摘要：常用于检测与多因素疾病易感性或抗性有关的基因的三种遗传学方法：非参数连锁分析、病例对照关联分析和传递不平衡检验。在这篇综述中，我们提出了这样的理论基础：如果患者和对照之间没有群体分层，病例对照关联研究具有最高的检测疾病基因的功效。利用高倍率的优势，我们对候选基因进行了广泛的病例对照关联分析，以在日本人和其他一些人群中寻找风湿病的易感基因。一些新的关联已被披露，包括 TNFR2、FCGR2B 和 CD19 基因多态性与系统性红斑狼疮的关联，此外还有一些意想不到的发现，例如健康人群中常见的 NKG2-C 无效等位基因。使用单核苷酸多态性 (SNP) 或微卫星多态性进行全基因组关联研究已成为现实，迫切需要开发新的高通量且经济有效的 SNP 分型技术。与此同时，我们的观察可能表明，即使在“后基因组测序”时代，“经典”候选基因方法仍将是一个强有力的替代方案。
Summary: There are three genetic methods often used for detecting genes contributing to susceptibility or resistance to multifactorial diseases: nonparametric linkage analysis, case–control association analysis, and transmission disequilibrium test. In this review, we present the theoretical basis that the case–control association study has the highest power of detecting disease genes if there is no population stratification between patients and controls. Taking advantage of the high power, we have carried out extensive case–control association analyses of candidate genes for the search of susceptibility genes to rheumatic diseases in the Japanese as well as in some other populations. Several new associations have been disclosed, including those of TNFR2, FCGR2B, and CD19 gene polymorphisms with systemic lupus erythematosus, in addition to some unexpected findings such as the common occurrence of NKG2‐C null allele in the healthy population. Genome‐wide association studies using single nucleotide polymorphisms (SNPs) or microsatellite polymorphisms have become realistic, and development of new high‐throughput and cost‐effective SNP typing technologies is urgently needed. At the same time, our observations may indicate that the ‘classical’ candidate gene approach will remain a strong alternative, even in the age of ‘post genome‐sequence’.