Network properties of genes harboring inherited disease mutations
Network properties of genes harboring inherited disease mutations
复制标题
DOI：
10.1073/pnas.0701722105
复制
发表时间：
2008-03-18
影响因子：
11.1
通讯作者：
Vitkup, Dennis
中科院分区：
文献类型：
--
作者：
Feldman, Igor;Rzhetsky, Andrey;Vitkup, Dennis
通过同时分析大量来自文献的以及高通量实验的数据集，我们在分子相互作用网络的背景下研究携带人类遗传性疾病突变的基因。我们的结果表明，网络特性影响疾病突变的可能性及其表型后果。具有中等连接性的基因携带生殖系疾病突变的概率最高，这表明疾病基因就其生理和细胞重要性而言往往占据一个中间位置。我们对组织表达谱的分析支持这一观点。我们表明，与所有人类基因相比，疾病突变在必需基因中发生的可能性较小。疾病基因在分析的分子网络中显示出显著的功能聚类。对于约三分之一已知的有两个或更多相关基因的疾病，我们发现具有相同表型的基因的物理聚类。这些聚类很可能代表疾病特异性功能模块，并为识别尚未发现的疾病基因提供了一个框架。
By analyzing, in parallel, large literature-derived and high-throughput experimental datasets we investigate genes harboring human inherited disease mutations in the context of molecular interaction networks. Our results demonstrate that network properties influence the likelihood and phenotypic consequences of disease mutations. Genes with intermediate connectivities have the highest probability of harboring germ-line disease mutations, suggesting that disease genes tend to occupy an intermediate niche in terms of their physiological and cellular importance. Our analysis of tissue expression profiles supports this view. We show that disease mutations are less likely to occur in essential genes compared with all human genes. Disease genes display significant functional clustering in the analyzed molecular network. For about one-third of known disorders with two or more associated genes we find physical clusters of genes with the same phenotype. These clusters are likely to represent disorder-specific functional modules and suggest a framework for identifying yet-undiscovered disease genes.