Ryu Ha-Jung, Jung Ho-Youl, Park Jung-Sun, Ryu Gil-Mi, Heo Jee Yeon, Kim Jae-Jung, Moon Song-Mean, Kim Hung-Tae, Lee Jong-Young, Koh Insong, Kim Jun-Woo, Rho Jae Kyun, Han Bok-Ghee, Kim Hyungtae, Park Choon-Sik, Oh Bermseok, Park Chan, Lee Jong-Keuk, Kimm Kuchan
National Genome Research Institute, National Institute of Health, Seoul, and Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University Hospital, Gyeonggi-Do, Korea.
Int Arch Allergy Immunol. 2006;139(3):209-16. doi: 10.1159/000091166. Epub 2006 Jan 27.
Numerous genetic studies have mapped asthma susceptibility genes to a region on chromosome 5q31-33 in several populations. This region contains a cluster of cytokines and other immune-related genes important in immune response. In the present study, to determine the genetic variations and patterns of linkage disequilibrium (LD), we resequenced all the exons and promoter regions of the 29 asthma candidate genes in the chromosome 5q31-33 region.
We identified a total of 314 genetic variants, including 289 single nucleotide polymorphisms (SNPs), 22 insertion/deletion polymorphisms and 3 microsatellites. Standardized variance data for allele frequency revealed substantial differences in SNP allele frequencies among different ethnic groups. Interestingly, significant ethnic differences were observed mainly in intron SNPs. LD block analysis using 174 common SNPs with a frequency of >10% disclosed strong LD within most candidate genes. No significant LD was observed across genes, except for one LD block (CD14-IK block). Gene-based haplotype analyses showed that 1-5 haplotype-tagging SNPs may be used to define the six or fewer common haplotypes with a frequency of >5%, regardless of the number of SNPs.
Overall, our results provide useful information for the identification of immune-mediated disease genes in the chromosome 5q31-33 region, as well as valuable evidence for gene-based haplotype analysis in disease association studies.
众多基因研究已将哮喘易感基因定位到多个群体中5号染色体q31 - 33区域。该区域包含一组在免疫反应中起重要作用的细胞因子和其他免疫相关基因。在本研究中，为了确定基因变异和连锁不平衡（LD）模式，我们对5号染色体q31 - 33区域内29个哮喘候选基因的所有外显子和启动子区域进行了重测序。
我们共鉴定出314个基因变异，包括289个单核苷酸多态性（SNP）、22个插入/缺失多态性和3个微卫星。等位基因频率的标准化方差数据显示不同种族群体的SNP等位基因频率存在显著差异。有趣的是，显著的种族差异主要在内含子SNP中观察到。使用174个频率>10%的常见SNP进行的LD块分析显示，大多数候选基因内存在强LD。除了一个LD块（CD14 - IK块）外，跨基因未观察到显著的LD。基于基因的单倍型分析表明，无论SNP数量如何，1 - 5个单倍型标签SNP可用于定义频率>5%的六个或更少的常见单倍型。
总体而言，我们的结果为鉴定5号染色体q31 - 33区域内的免疫介导疾病基因提供了有用信息，也为疾病关联研究中基于基因的单倍型分析提供了有价值的证据。
