Hartmann Linda, Theiss Stephan, Niederacher Dieter, Schaal Heiner
Heinrich-Heine-University Duesseldorf, Institute for Virology, D-40225 Duesseldorf, Germany.
Front Biosci. 2008 May 1;13:3252-72. doi: 10.2741/2924.
Pathogenic splicing alterations caused by point mutations in both splice sites and auxiliary cis-regulatory elements are increasingly recognized as an important mechanism through which gene mutations cause human disease. Unfortunately, in routine genetic diagnostic settings, splicing mutations may escape identification, due to the lack of RNA samples. Since most patients are genotyped only, any computational prediction of mutation effects on splicing can be beneficial for the human geneticist. Here, we review common techniques to identify human point mutations and delineate the molecular basis for splice site recognition. Moreover, this article provides basic insights into web-tools predicting splice sites and cis-regulatory elements and discusses their benefits for judgment of clinically identified sequence variants of disease-specific genes.
剪接位点和辅助顺式调控元件中的点突变所导致的致病性剪接改变，日益被视为基因突变引发人类疾病的一种重要机制。遗憾的是，在常规基因诊断环境中，由于缺乏RNA样本，剪接突变可能无法被识别。由于大多数患者仅进行基因分型，因此任何关于突变对剪接影响的计算预测，对人类遗传学家而言都可能有所助益。在此，我们综述了识别人类点突变的常用技术，并阐述了剪接位点识别的分子基础。此外，本文还提供了对预测剪接位点和顺式调控元件的网络工具的基本见解，并讨论了它们对于判断疾病特异性基因的临床鉴定序列变异的益处。
