title: mirDNMR: a gene-centered database of background de novo mutation rates in human.
abstract: De novo germline mutations (DNMs) are the rarest genetic variants proven to cause a considerable number of sporadic genetic diseases, such as autism spectrum disorders, epileptic encephalopathy, schizophrenia, congenital heart disease, type 1 diabetes, and hearing loss. However, it is difficult to accurately assess the cause of DNMs and identify disease-causing genes from the considerable number of DNMs in probands. A common method to this problem is to identify genes that harbor significantly more DNMs than expected by chance, with accurate background DNM rate (DNMR) required. Therefore, in this study, we developed a novel database named mirDNMR for the collection of gene-centered background DNMRs obtained from different methods and population variation data. The database has the following functions: (i) browse and search the background DNMRs of each gene predicted by four different methods, including GC content (DNMR-GC), sequence context (DNMR-SC), multiple factors (DNMR-MF) and local DNA methylation level (DNMR-DM); (ii) search variant frequencies in publicly available databases, including ExAC, ESP6500, UK10K, 1000G and dbSNP and (iii) investigate the DNM burden to prioritize candidate genes based on the four background DNMRs using three statistical methods (TADA, Binomial and Poisson test). As a case study, we successfully employed our database in candidate gene prioritization for a sporadic complex disease: intellectual disability. In conclusion, mirDNMR (https://www.wzgenomics.cn/mirdnmr/) can be widely used to identify the genetic basis of sporadic genetic diseases.
authors: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, China.
authors: Yi
authors: Y
authors: Jiang
authors: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, China.
authors: Zhongshan
authors: Z
authors: Li
authors: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, China.
authors: Zhenwei
authors: Z
authors: Liu
authors: Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325000, China.
authors: Denghui
authors: D
authors: Chen
authors: Beijing Institutes of Life Science, Chinese Academy of Science, Beijing 100101, China.
authors: Wanying
authors: W
authors: Wu
authors: Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325000, China.
authors: Yaoqiang
authors: Y
authors: Du
authors: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, China.
authors: Liying
authors: L
authors: Ji
authors: The Eye Hospital of Wenzhou Medical University, The State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health, Wenzhou 325000, China.
authors: Zi-Bing
authors: ZB
authors: Jin
authors: Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325000, China liweiwzmc@163.com.
authors: Wei
authors: W
authors: Li
authors: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, China iamwujy@gmail.com.
authors: Jinyu
authors: J
authors: Wu
mesh_terms: D019295:Computational Biology / Q000379:methods; D030561:Databases, Nucleic Acid; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods; D018095:Germ-Line Mutation; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D059645:Mutation Rate; D014584:User-Computer Interface; D064878:Web Browser