UMD-USHbases: a comprehensive set of databases to record and analyse pathogenic mutations and unclassified variants in seven Usher syndrome causing genes.
UMD-USHbases: a comprehensive set of databases to record and analyse pathogenic mutations and unclassified variants in seven Usher syndrome causing genes.
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DOI：
10.1002/humu.20780
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发表时间：
2008-08-01
期刊：
影响因子：
3.9
通讯作者：
Roux, Anne-Francoise
中科院分区：
文献类型：
--
作者：
Baux, David;Faugere, Valerie;Roux, Anne-Francoise
利用通用突变数据库(UMD)软件构建了Usher综合征相关基因(MYO7A、CDH23、PCDH15、USH1C、USH1G、USH3A和USH2A)的核苷酸变异关系型数据库UMD-USHbase。在非综合征性听力损失病例中也记录了导致Usher综合征I型基因的突变，在非综合征性视网膜色素变性中也记录了USH2A突变。由于临床和分子的异质性，Usher综合征给分子诊断学带来了特殊的挑战。由于许多突变都是错义变化，而且所有的基因都含有明显的非致病基因多态，良好的数据库对于准确解释致病性至关重要。提供了评估突变致病性的工具，包括氨基酸的保守性和剪接点的分析。提供了参考氨基酸比对。Usher综合征患者在核苷酸和氨基酸水平上的明显非致病变异都包括在内。UMD-USH数据库目前包含2,830多个条目，包括在938多名患者中发现的致病突变、未分类变异或非致病性多态。除了从89个出版物收集的数据外，在我们实验室中发现的15个新突变被记录在MYO7A(6)、CDH23(8)或PCDH15(1)基因中。提供了关于这七个基因的相对参与程度、每个基因中变异的数量和分布的信息。UMD-USHbase允许访问提供特定例程和优化的多标准研究和分类工具的软件包。这些数据库应该有助于临床医生和遗传学家寻找与亚瑟综合征相关的突变信息。
Using the Universal Mutation Database (UMD) software, we have constructed "UMD-USHbases", a set of relational databases of nucleotide variations for seven genes involved in Usher syndrome (MYO7A, CDH23, PCDH15, USH1C, USH1G, USH3A and USH2A). Mutations in the Usher syndrome type I causing genes are also recorded in non-syndromic hearing loss cases and mutations in USH2A in non-syndromic retinitis pigmentosa. Usher syndrome provides a particular challenge for molecular diagnostics because of the clinical and molecular heterogeneity. As many mutations are missense changes, and all the genes also contain apparently non-pathogenic polymorphisms, well-curated databases are crucial for accurate interpretation of pathogenicity. Tools are provided to assess the pathogenicity of mutations, including conservation of amino acids and analysis of splice-sites. Reference amino acid alignments are provided. Apparently non-pathogenic variants in patients with Usher syndrome, at both the nucleotide and amino acid level, are included. The UMD-USHbases currently contain more than 2,830 entries including disease causing mutations, unclassified variants or non-pathogenic polymorphisms identified in over 938 patients. In addition to data collected from 89 publications, 15 novel mutations identified in our laboratory are recorded in MYO7A (6), CDH23 (8), or PCDH15 (1) genes. Information is given on the relative involvement of the seven genes, the number and distribution of variants in each gene. UMD-USHbases give access to a software package that provides specific routines and optimized multicriteria research and sorting tools. These databases should assist clinicians and geneticists seeking information about mutations responsible for Usher syndrome.