Sudandiradoss C, Sethumadhavan Rao
Bioinformatics Division, School of Biotechnology, Chemical and Biomedical Engineering, Vellore Institute of Technology, Vellore, TN, 632014, India.
Genomic Med. 2008 Dec;2(3-4):55-67. doi: 10.1007/s11568-009-9027-3. Epub 2009 Feb 12.
Single-nucleotide polymorphisms (SNPs) play a major role in the understanding of the genetic basis of many complex human diseases. It is still a major challenge to identify the functional SNPs in disease-related genes. In this review, the genetic variation that can alter the expression and the function of the genes, namely KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2, with the potential role for the development of congenital long QT syndrome (LQTS) was analyzed. Of the total of 3,309 SNPs in all five genes, 27 non-synonymous SNPs (nsSNPs) in the coding region and 44 SNPs in the 5' and 3' un-translated regions (UTR) were identified as functionally significant. SIFT and PolyPhen programs were used to analyze the nsSNPs and FastSNP; UTR scan programs were used to compute SNPs in the 5' and 3' untranslated regions. Of the five selected genes, KCNQ1 has the highest number of 26 haplotype blocks and 6 tag SNPs with a complete linkage disequilibrium value. The gene SCN5A has ten haplotype blocks and four tag SNPs. Both KCNE1 and KCNE2 genes have only one haplotype block and four tag SNPs. Four haplotype blocks and two tag SNPs were obtained for KCNH2 gene. Also, this review reports the copy number variations (CNVs), expressed sequence tags (ESTs) and genome survey sequences (GSS) of the selected genes. These computational methods are in good agreement with experimental works reported earlier concerning LQTS.
单核苷酸多态性（SNP）在理解许多复杂人类疾病的遗传基础方面发挥着重要作用。识别疾病相关基因中的功能性SNP仍然是一项重大挑战。在本综述中，分析了可能改变基因（即KCNQ1、KCNH2、SCN5A、KCNE1和KCNE2）表达和功能的遗传变异，这些变异对先天性长QT综合征（LQTS）的发生发展具有潜在作用。在所有五个基因的总共3309个SNP中，编码区的27个非同义SNP（nsSNP）以及5'和3'非翻译区（UTR）的44个SNP被确定为具有功能意义。使用SIFT和PolyPhen程序分析nsSNP，并使用FastSNP；UTR扫描程序用于计算5'和3'非翻译区的SNP。在所选的五个基因中，KCNQ1具有最多的26个单倍型块和6个标签SNP，其完全连锁不平衡值最高。SCN5A基因有10个单倍型块和4个标签SNP。KCNE1和KCNE2基因都只有1个单倍型块和4个标签SNP。KCNH2基因获得了四个单倍型块和两个标签SNP。此外，本综述还报告了所选基因的拷贝数变异（CNV）、表达序列标签（EST）和基因组调查序列（GSS）。这些计算方法与先前报道的有关LQTS的实验工作高度一致。
