Chang H, Fujita T
Health Service Center, Department of Internal Medicine, University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
Biochem Biophys Res Commun. 2001 Sep 14;287(1):288-91. doi: 10.1006/bbrc.2001.5576.
Recent progress in identification and mapping of single nucleotide polymorphisms (SNPs) in the human genome generates an unprecedented opportunity to explore cause-effect relationships between genetic variations and susceptibility to common diseases. For this purpose, one promising strategy would be to select a set of SNPs that potentially alter the function of proteins involved in the pathogenesis of the diseases and compare their frequencies in the affected individuals and the healthy population. In this respect, SNPs that change amino acid sequences (nonsynonymous SNPs; nsSNPs) are of particular interest, since they are more likely to affect protein functions. In this study, we have constructed a catalog of nsSNPs (PicSNP), whose unique features are (i) nsSNPs are classified according to the functions of the affected genes and are searchable under the guidance of hierarchical lists of protein functions and (ii) nsSNPs that lead to amino acid changes in the known functional sites and domains of proteins are highlighted. Out of 1,190,295 SNPs extracted from public database, we identified 3793 nsSNPs and classified them in 1247 categories of protein functions. 495 sites and domains annotated in the Swiss-Prot database were found to include nsSNPs, including 2 nsSNPs in disulfide-binding sites and 38 nsSNPs in transmembrane regions. PicSNP is available via the World Wide Web (http://picsnp.org) and would support research questing for SNPs involved in common diseases.
人类基因组中单个核苷酸多态性（SNP）的识别与定位研究取得的最新进展，为探索基因变异与常见疾病易感性之间的因果关系带来了前所未有的机遇。为此，一个有前景的策略是选择一组可能改变参与疾病发病机制的蛋白质功能的SNP，并比较它们在患病个体和健康人群中的频率。在这方面，改变氨基酸序列的SNP（非同义SNP；nsSNP）特别受关注，因为它们更有可能影响蛋白质功能。在本研究中，我们构建了一个nsSNP目录（PicSNP），其独特之处在于：（i）nsSNP根据受影响基因的功能进行分类，并可在蛋白质功能层次列表的指导下进行搜索；（ii）导致蛋白质已知功能位点和结构域氨基酸变化的nsSNP会被突出显示。从公共数据库中提取的1,190,295个SNP中，我们识别出3793个nsSNP，并将它们分类到1247个蛋白质功能类别中。发现Swiss-Prot数据库中注释的495个位点和结构域包含nsSNP，其中包括2个位于二硫键结合位点的nsSNP和38个位于跨膜区域的nsSNP。可通过万维网（http://picsnp.org）获取PicSNP，它将支持对参与常见疾病的SNP的研究探索。
