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

1.单基因疾病致病基因突变数据的汇编和知识库建设：数据以KMDB格式构建，KMDB是为此目的而创建的。总数据量已经增长到259个基因、407个疾病和10166个突变案例(本研究开始时的初始数据量分别为149个基因、144个疾病和3738个突变案例)。数据类别扩大到以下11个部分：遗传性眼病、听力障碍、心血管系统/心脏疾病、肌肉疾病、脑/神经疾病、血液系统疾病、肾脏疾病、综合征疾病、自身免疫、家族性肿瘤和骨骼发育不良。还对类似疾病组进行了广泛的数据收集，例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)。收集多态数据：从包括HGBAS…在内的公共数据库中提取单基因疾病中发现的多态更多E和DBSNP并设置为kmdb。以HLA等典型病例为例，探讨了构建多因素疾病多态数据知识库的途径和方法。通过实验从实际临床病例中寻找突变数据：分析滨松大学医学院以下疾病的突变情况：光敏性疾病、眼底白斑、斜视和蓝锥体单色性。在白点眼底鱼中发现了一种新的RDH5基因突变。在光敏性疾病方面，从世界上第四例日本首例毛发硫代营养不良(TTD-A)患者中发现了一种新的TFB5基因突变。此外，在圆锥干畸形脸部综合征病例中发现了TBX1基因的突变，证明该基因是该病的致病基因。最后一项是与东京女子医科大学的一个小组合作完成的。(构建的知识库可以从http://mutview.dmb.med.keio.ac.jp/)Less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