Skeleton Genetics: a comprehensive database for genes and mutations related to genetic skeletal disorders

Abstract

Genetic skeletal disorders (GSD) involving the skeletal system arises through disturbances in the complex processes of skeletal development, growth and homeostasis and remain a diagnostic challenge because of their clinical heterogeneity and genetic variety. Over the past decades, tremendous effort platforms have been made to explore the complex heterogeneity, and massive new genes and mutations have been identified in different GSD, but the information supplied by literature is still limited and it is hard to meet the further needs of scientists and clinicians. In this study, combined with Nosology and Classification of genetic skeletal disorders, we developed the first comprehensive and annotated genetic skeletal disorders database, named 'SkeletonGenetics', which contains information about all GSD-related knowledge including 8225 mutations in 357 genes, with detailed information associated with 481 clinical diseases (2260 clinical phenotype) classified in 42 groups defined by molecular, biochemical and/or radiographic criteria from 1698 publications. Further annotations were performed to each entry including Gene Ontology, pathways analysis, protein-protein interaction, mutation annotations, disease-disease clustering and gene-disease networking. Furthermore, using concise search methods, intuitive graphical displays, convenient browsing functions and constantly updatable features, 'SkeletonGenetics' could serve as a central and integrative database for unveiling the genetic and pathways pre-dispositions of GSD.Database URL: http://101.200.211.232/skeletongenetics/.

Figure 1.

Flowchart of the procedure for ‘SkeletonGenetics’. ‘SkeletonGenetics’ mainly consists of three parts: (i) data extraction based on literature search and GSD-related databases, (ii) annotation of all mutations and genes using ANNOVAR and (iii) enrichment analysis by WebGestalt and gene–disease network analysis graphically.

Figure 2.

A screenshot of the search, browse and annotation module in ‘SkeletonGenetics’. Search box at home page for searching by five symbols. ‘gene symbol’, ‘gene ID’ and ‘gene transcript’, ‘mutations position’ and phenotype information. ‘Browse by chromosome’ is used to retrieve all GSD-related genes mapped on chromosomes, ‘Browse by disease’ is used to retrieve all GSD-related genes’. Annotation module including functional and enrichment analysis, mutation annotation, mutation spectrum and gene–disease network.