Human non-synonymous SNPs: server and survey
Human non-synonymous SNPs: server and survey
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DOI：
10.1093/nar/gkf493
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发表时间：
2002-09-01
影响因子：
14.9
通讯作者：
Sunyaev, S
中科院分区：
文献类型：
--
作者：
Ramensky, V;Bork, P;Sunyaev, S
人类单核苷酸多态性（SNP）代表了人类群体DNA变异的最常见类型。SNP研究的主要目标之一是了解人类表型变异的遗传学，特别是人类复杂疾病的遗传基础。非同义编码SNP（nsSNP）包括一组SNP，其与调节区中的SNP一起被认为对表型具有最高影响。在这里，我们提出了一个万维网服务器来预测nsSNP对蛋白质结构和功能的影响。该预测方法使得能够分析公开可用的SNP数据库HGVbase，这产生了具有预测功能的nsSNP数据集。该数据集进一步用于比较负责nsSNP表型展示的氨基酸取代的各种结构和功能特征的影响。我们还研究了选择压力对蛋白质结构和功能性质的依赖性。我们发现，在我们的数据集中，针对有害SNP的选择压力取决于蛋白质的分子功能，尽管它对所考虑的其他几种蛋白质特征不敏感。对于参与转录调节的蛋白质，检测到最强的选择压力。
Human single nucleotide polymorphisms (SNPs) represent the most frequent type of human population DNA variation. One of the main goals of SNP research is to understand the genetics of the human phenotype variation and especially the genetic basis of human complex diseases. Non-synonymous coding SNPs (nsSNPs) comprise a group of SNPs that, together with SNPs in regulatory regions, are believed to have the highest impact on phenotype. Here we present a World Wide Web server to predict the effect of an nsSNP on protein structure and function. The prediction method enabled analysis of the publicly available SNP database HGVbase, which gave rise to a dataset of nsSNPs with predicted functionality. The dataset was further used to compare the effect of various structural and functional characteristics of amino acid substitutions responsible for phenotypic display of nsSNPs. We also studied the dependence of selective pressure on the structural and functional properties of proteins. We found that in our dataset the selection pressure against deleterious SNPs depends on the molecular function of the protein, although it is insensitive to several other protein features considered. The strongest selective pressure was detected for proteins involved in transcription regulation.