Department of Medical Genetics, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia,
Mol Genet Genomics. 2014 Jun;289(3):469-87. doi: 10.1007/s00438-014-0826-4. Epub 2014 Feb 22.
We screened for the major essential single-nucleotide polymorphism (SNP) variant that might be associated with the MSH2 gene based on the data available from three types of human tissue samples [156 lymphoblastoid cell variations (LCL), 160 epidermis, 166 fat]. An association analysis confirmed that the KCNK12 SNP variant (rs748780) was highly associated (p value 9 × 10(-4)) with the MSH2 gene for all three samples. Using SNP identification, we further found that the recognized SNP was also relevant among Hapmap populations. Techniques that display specific SNPs associated with the gene of interest or nearby genes provide more reliable genetic associations than techniques that rely on data from individual SNPs. We investigated the MSH2 gene regional linkage association with the determined SNP (rs748780), KCNK12 variant (Allele T>C) in the intronic region, in HapMap3 full dataset populations, Yoruba in Ibadan, Nigeria (YRI), Utah residents with ancestry from northern Europe (CEU), Han Chinese in Beijing, China (CHB), and a population of Mexican ancestry in Los Angeles, California (MEX). A gene-based SNP association analysis analyzes the combined impact of every variant within the gene while creating referrals to linkage disequilibrium or connections between markers. Our results indicated that among the four populations studied, this association was highest in the MEX population based on the r(2) value; a similar pattern was also observed in the other three populations. The relevant SNP rs748780 in KCNK12 is related to a superfamily of potassium channel pore-forming P-domain proteins as well as to other non-pore-forming proteins and has been shown to be relevant to neurological disorder predisposition in MEX as well as in other populations.
我们基于三种人体组织样本[156 个淋巴母细胞变异体(LCL)、160 个表皮、166 个脂肪]中的数据,筛选了可能与 MSH2 基因相关的主要必需单核苷酸多态性(SNP)变体。关联分析证实,KCNK12 SNP 变体(rs748780)与所有三种样本的 MSH2 基因高度相关(p 值为 9×10(-4))。使用 SNP 鉴定,我们进一步发现该公认的 SNP 也与 Hapmap 人群相关。与感兴趣的基因或附近基因相关的特定 SNP 显示技术比依赖于单个 SNP 数据的技术提供更可靠的遗传关联。我们调查了 MSH2 基因区域与确定的 SNP(rs748780)的连锁关联,该 SNP 位于 KCNK12 变体(内含子区域的等位基因 T>C),在 HapMap3 全数据集人群中,尼日利亚伊巴丹的约鲁巴人(YRI)、来自北欧的犹他州居民(CEU)、中国北京的汉族人(CHB)和加利福尼亚洛杉矶的墨西哥裔美国人(MEX)。基于基因的 SNP 关联分析分析了基因内每个变体的综合影响,同时参考了连锁不平衡或标记之间的联系。我们的结果表明,在所研究的四个群体中,基于 r(2) 值,这种关联在 MEX 群体中最高,其他三个群体也观察到了类似的模式。KCNK12 中的相关 SNP rs748780 与钾通道孔形成 P 结构域蛋白的超家族以及其他非孔形成蛋白有关,并且已被证明与 MEX 以及其他人群的神经障碍易感性有关。