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

点击翻译按钮获取中文摘要

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