Year: 2015
Type: article
Abstract: The globalization of genetic variant databases associated with single gene disorders has been ongoing for several decades, usually in the form of locus specific databases (LSDBs) curated by a single individual or research group. The inclusion of a variant into a specific LSDB was usually limited to those published in the literature or identified through the curator's own research on the disease. The databasing of disease-producing variants has now been expanded, as seen in the Human Gene Mutation Database (HGMD), which collects variants for known disease genes from the literature, or the Lieden Open Variation Database (LOVD), where essentially multiple expert-curated LSDBs have been aggregated into a single large database. In this issue, Bladen and co-workers (Hum Mutat 36:395–402, 2015) have created a world-wide consortium to identify variants associated with Duchenne Muscular Dystrophy (DMD), an X-linked neuromuscular disease. To date, an impressive 7,150 variants associated with DMD have been entered into the TREAT-NMD DMD Global database, part of the TREAT-NMD Neuromuscular Network. It contains the single largest cohort of verified DMD mutations publicly available. The database is curated and augmented by 30 national mutation registries, with variants contributed by 61 individuals representing 44 institutions throughout the world. HGVS nomenclature is used to describe variants associated with DMD and the milder form of muscular dystrophy, Becker muscular dystrophy (BMD). The database is searchable and contains additional data including phenotypic information, results of dystrophin analysis by immunofluorescence and western blot based techniques, type of genetic transmission (e.g. de novo or germline variants), and references including publications, posters and personal communications. The curators are also attempting to link novel DMD therapies that are mutation type-specific to those individuals with mutations that may respond to therapy. For example, 10% of DMD mutations are nonsense mutations that may respond to stop codon read-through therapy. The creation of the TREAT-NMD DMD Global database underscores the complexity of “simple” single locus Mendelian diseases and showcases the importance of worldwide consortia in the curation of these types of repositories to ensure that all population based variation is represented. There is every reason to conclude that this type of effort will be needed for all genetic disorders, to make sure that mutations from all populations are collected. This level of effort will also be needed for variants associated with complex multi-locus-based diseases.
Source: Human Mutation
DOI: 10.1002/humu.22780
Author: William S. Oetting
Institution: University of Minnesota
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2046444196