Bae Joon Seol, Cheong Hyun Sub, Kim Ji-On, Lee Soo Ok, Kim Eun Mi, Lee Hye Won, Kim Sangsoo, Kim Ji-woong, Cui Tailin, Inoue Ituro, Shin Hyoung Doo
Department of Genetic Epidemiology, SNP Genetics, Inc., Room 1407, Complex B, WooLim Lion's Valley, 371-28, Gasan-Dong, Geumcheon-Gu, Seoul 153-801, Republic of Korea.
Biochem Biophys Res Commun. 2008 Sep 5;373(4):593-6. doi: 10.1016/j.bbrc.2008.06.083. Epub 2008 Jul 2.
Copy number variation (CNV) is emerging as a new tool for understanding human genomic variation, but its relationship with human disease is not yet fully understood. The data for a total of 317,503 genotypes were collected for a genome-wide association study of subarachnoid aneurismal hemorrhage (SAH) in a Japanese population (cases and controls, n=497) using Illumina HumanHap300 BeadChip. To identify multi-allelic CNV markers, we visually inspected all genotype clusters of 317,503 SNP markers covering the whole genome using Illumina's BeadStudio 3.0 software. As a result, we identified 597 multi-allelic CNV markers for common (copy loss frequency>0.05) CNV regions in a Japanese population (n=497). The identified CNV markers shared the following characteristics: enrichment of Hardy-Weinberg disequilibria, Mendelian inconsistency among families, and high missing genotype rate. All annotated information for those markers is summarized in our database (http://www.snp-genetics.com/user/srch.htm). In addition, we performed case-control association analyses of identified multi-allelic CNV markers with the risk of subarachnoid aneurysmal hemorrhage. One SNP marker (rs1242541) within a CNV region neighboring the Sel-1 suppressor of lin-12-like protein (SEL1L) was significantly associated with a risk of SAH (P=0.0006). We also validated the CNV around rs1242541 using real-time quantitative polymerase chain reaction (PCR). Information and methods used in this study would be helpful for accurate genotyping of SNPs on CNV regions, which could be used for association analysis of SNP markers within CNV regions.
拷贝数变异（CNV）正在成为一种理解人类基因组变异的新工具，但其与人类疾病的关系尚未完全明确。我们使用Illumina HumanHap300 BeadChip，针对日本人群（病例和对照，n = 497）的蛛网膜下腔动脉瘤性出血（SAH）进行全基因组关联研究，收集了总共317,503个基因型的数据。为了识别多等位基因CNV标记，我们使用Illumina的BeadStudio 3.0软件，对覆盖整个基因组的317,503个SNP标记的所有基因型簇进行了目视检查。结果，我们在日本人群（n = 497）中识别出597个常见（拷贝数缺失频率>0.05）CNV区域的多等位基因CNV标记。所识别的CNV标记具有以下共同特征：哈迪-温伯格不平衡富集、家族内孟德尔不一致性以及高基因型缺失率。这些标记的所有注释信息都汇总在我们的数据库中（http://www.snp-genetics.com/user/srch.htm）。此外，我们对所识别的多等位基因CNV标记与蛛网膜下腔动脉瘤性出血风险进行了病例对照关联分析。一个位于类lin-12样蛋白（SEL1L）的Sel-1抑制因子附近CNV区域内的SNP标记（rs1242541）与SAH风险显著相关（P = 0.0006）。我们还使用实时定量聚合酶链反应（PCR）验证了rs1242541周围的CNV。本研究中使用的信息和方法将有助于对CNV区域的SNP进行准确基因分型，可用于CNV区域内SNP标记的关联分析。
