PDF(Pubmed)
Abstract：
The study of rare diseases is important not only for the individuals affected but also for the advancement of medical knowledge and a deeper understanding of human biology and genetics. The wide repertoire of structural information now available from reliable and accurate prediction methods provides the opportunity to investigate the molecular origins of most of the rare diseases reviewed in the Orpha.net database. Thus, it has been possible to analyze the topology of the pathogenic missense variants found in the 2515 proteins involved in Mendelian rare diseases (MRDs), which form the database for our structural bioinformatics study. The amino acid substitutions responsible for MRDs showed different mutation site distributions at different three-dimensional protein depths. We then highlighted the depth-dependent effects of pathogenic variants for the 20,061 pathogenic variants that are present in our database. The results of this structural bioinformatics investigation are relevant, as they provide additional clues to mitigate the damage caused by MRD.
摘要：
罕见疾病的研究不仅对受影响的个体很重要，而且对医学知识的进步以及对人类生物学和遗传学的更深入理解也很重要。现在可以从可靠和准确的预测方法中获得广泛的结构信息，为研究Orpha.net数据库中审查的大多数罕见疾病的分子起源提供了机会。因此，有可能分析在涉及孟德尔罕见疾病（MRD）的2515种蛋白质中发现的致病性错义变体的拓扑结构，构成了我们结构生物信息学研究的数据库。负责MRD的氨基酸取代在不同的三维蛋白质深度显示不同的突变位点分布。然后，我们强调了我们数据库中存在的20,061个致病变体的致病变体的深度依赖性效应。这项结构生物信息学调查的结果是相关的，因为它们提供了额外的线索来减轻MRD造成的损害。
