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

1. 汇编单基因疾病相关基因的突变数据和建立知识库：数据是以以前为此目的创建的KMDB格式构建的。总数据量已增至259个基因，407种疾病，10166例突变（本研究开始时初始数据量分别为149个基因，144种疾病，3738例突变）。数据类别扩展到以下11个部分：遗传性眼病、听力缺陷、心血管系统/心脏疾病、肌肉疾病、脑/神经元疾病、血液系统疾病、肾脏疾病、综合征疾病、自身免疫性、家族性肿瘤和骨骼发育不良。对类似疾病组进行了广泛的数据收集，如非综合征性听力损失（55个致病基因）和视网膜色素变性（33个致病基因）。收集多态性数据：从HGBAS、More E和dbSNP等公共数据库中提取单基因疾病的多态性，并设置到KMDB中。以hla为例，探讨了构建多因子疾病多态数据知识库的方法和途径。通过实验从实际临床病例中检索突变数据：对滨松大学医学院以下疾病的病例进行突变分析：光敏性疾病、白点眼底、斜视、蓝锥单色。在白斑眼底发现了一个新的RDH5基因突变。在光敏性疾病中，从日本第一例（世界上第4例）毛硫营养不良（TTD-A）病例中发现了TFB5基因突变。此外，从圆锥锥体异常脸综合征病例中鉴定出TBX1基因突变，证明该基因是该疾病的一个原因。最后一项是与东京女子医科大学的一个小组合作完成的。(构建的知识库可从http://mutview.dmb.med.keio.ac.jp/访问

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