Construction of an integrated knowledge-base for mutations in disease-responsible genes and polymorphisms in disease-related genes

疾病相关基因突变和疾病相关基因多态性综合知识库的构建

基本信息

批准号：
14013053
负责人：
MINOSHIMA Shinsei
金额：
$ 17.09万
依托单位：
Hamamatsu University School of Medicine (2003-2004)Keio University (2002)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

1. Compiling mutation data of responsible genes for monogenic diseases and knowledge-base construction: Data were constructed in a format of KMDB which has been previously created for this purpose. Total data amount has grown to 259 genes, 407 diseases and 10166 mutation cases (initial data amount at the beginning of this research was 149 genes, 144 diseases and 3738 mutation cases, respectively). Data category was expanded to the following 11 sections: hereditary eye diseases, hearing defects, cardiovascular system/heart diseases, muscle diseases, brain/neuronal diseases, blood system diseases, kidney disorders, syndromic diseases, autoimmune, familial tumors, and skeletal dysplasias. Extensive data gathering for groups of similar diseases was also performed such as non-syndromic hearing loss (55 causative genes) and retinitis pigmentosum (33 causative genes).2. Collecting polymorphism data: Polymorphisms found in monogenic diseases were extracted from public databases including HGBAS … More E and dbSNP and set into KMDB. The ways and means to construct a knowledge-base of polymorphism data in multifactorial diseases was considered using model cases such as HLA.3. Search of mutation data from actual clinical cases by experiments: Cases of the following diseases in Hamamatsu University School of Medicine were analyzed for mutations: Photosensitivity diseases, fundus albipunctatus, strabismus, and blue cone monochromacy. For the fundus albipunctatus, a novel mutation in RDH5 gene was found. For the photosensitivity diseases, a novel mutation in TFB5 gene was found from the first Japanese case of trichothiodystrophy (TTD-A), which is the fourth case in the world. Further, mutations were identified from the TBX1 gene of conotruncal anomaly face syndrome cases, which proved that the gene is a responsible for the disease. The last was done as a collaboration with a group of Tokyo Women's Medical University.(Constructed knowledge-base is accessible from http://mutview.dmb.med.keio.ac.jp/) Less

1。编译单基因疾病和知识碱构建的负责基因的突变数据：数据以KMDB的格式构建，该格式以前是为此目的而创建的。总数据量已增长到259个基因，407种疾病和10166例突变病例（本研究开始时的初始数据量分别为149个基因，144种疾病和3738个突变病例）。数据类别扩展到以下11个部分：还进行了类似疾病组的广泛数据收集，例如非综合性听力损失（55个基因基因）和色素性视网膜炎（33个基因）.2。收集多态性数据：从HGBAS等公共数据库中提取了在单基因疾病中发现的多态性……更多的E和DBSNP并将其设置为KMDB。使用诸如HLA.3的模型案例，考虑了在多因素疾病中构建多态性数据知识基础的方法和手段。通过实验搜索来自实际临床病例的突变数据：分析了哈马马村大学医学院以下疾病的病例以进行突变：光敏性疾病，眼底障碍物，斜视和蓝锥单色。对于眼底膜虫，发现了RDH5基因中的新突变。对于光敏性疾病，从第一个日本的Trichothiodystrophophy（TTD-A）中发现了TFB5基因的新型突变，这是世界第四个病例。此外，从共鸣异常综合征病例的TBX1基因中鉴定出突变，这证明该基因是对疾病负责的。最后一个是与一群东京女子医科大学合作的。