Human disease genes: patterns and predictions
Human disease genes: patterns and predictions
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DOI：
10.1016/s0378-1119(03)00772-8
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发表时间：
2003-10-30
期刊：
影响因子：
3.5
通讯作者：
Eyre-Walker, A
中科院分区：
文献类型：
--
作者：
Smith, NGC;Eyre-Walker, A
我们比较了已知突变导致人类疾病的基因（疾病基因）与其他人类基因（非疾病基因），使用了大量的人类-啮齿动物比对来推断进化模式。这样的比较可能在预测疾病基因和理解人类基因的一般进化方面都有用处。发现疾病基因和非疾病基因之间有四个特征显著不同，疾病基因（i）以较高的非同义/同义替换率比（Ka/Ks）进化，（ii）以较高的同义替换率进化，（iii）具有较长的蛋白质编码序列，（iv）在较窄的组织范围内表达。判别分析表明，这些差异可能有助于预测人类疾病基因。我们还研究了影响疾病基因进化模式的其他因素：Ka/KS受到蛋白质功能、遗传模式以及疾病引起的预期寿命缩短的显着影响。(C)2003 Elsevier B. V.保留所有权利。
We compared genes at which mutations are known to cause human disease (disease genes) with other human genes (nondisease genes) using a large set of human-rodent alignments to infer evolutionary patterns. Such comparisons may be of use both in predicting disease genes and in understanding the general evolution of human genes. Four features were found to differ significantly between disease and nondisease genes, with disease genes (i) evolving with higher nonsynonymous/synonymous substitution rate ratios (Ka/Ks), (ii) evolving at higher synonymous substitution rates, (iii) with longer protein-coding sequences, and (iv) expressed in a narrower range of tissues. Discriminant analysis showed that these differences may help to predict human disease genes. We also investigated other factors affecting the mode of evolution in the disease genes: Ka/Ks is significantly affected by protein function, mode of inheritance, and the reduction of life expectancy caused by disease. (C) 2003 Elsevier B.V. All rights reserved.