遗传性牙本质疾病致病基因突变谱的生物信息学研究

Bioinformatic study of the spectrum of mutations for hereditary dentin defects

运用PolyPhen-2,SignalP 3.0,SplicePort等多种生物信息学软件对遗传性牙本质疾病致病基因(牙本质涎磷蛋白基因)突变谱进行总结和生物信息学分析。在已知60个患者家系中的40个突变中,发现19个错义突变或无义突变发生在DSP结构域,而21个移码突变发生在DPP结构域。在DSP结构域中,1个突变可能改变信号肽剪切位置;4个突变降低信号肽剪切的可能性;10个突变干扰外显子间的剪接;1个突变提前终止翻译过程;还有3个突变可能对多肽的空间结构产生影响。由于在DPP结构域的移码突变缺乏合适的分析软件,尚无法准确评估各个突变发生后的生物学效应。

Various bioinformatics software programs （ PolyPhen-2, SignalP 3.0 and SplicePort） were used to analyze the spectrum of mutations in DSPP gene for hereditary dentin defects. 40 mutations within DSPP for the hereditary dentin defects have been identified in 60 independent families. The 19 missense or nonsense mutations were located within the DSP domain, and 21 mutations located in the DPP domain cause frameshift mutations. In DSP domain, a mutation may change the cleavage site for the signal peptide; four mutations may affect signal peptide cleavage ; ten mutations may affect normal pre-mRNA splicing; a mutation can create a stop eodon; three mutatuons may di- rectly affect the biological function of DSP by changing its normal space conformation. Unfortunately, bioinformatic analysis was unavailable for the frameshift mutations within the DPP domain.