General mutation databases : analysis and review

Databases of mutations causing Mendelian disease play a crucial role in research, diagnostic and genetic health care and can play a role in life and death decisions. These databases are thus heavily used, but only gene or locus specific databases have been previously reviewed for completeness, accuracy, currency and utility. We have performed a review of the various general mutation databases that derive their data from the published literature and locus specific databases. Only two&mdash;the Human Gene Mutation Database (HGMD) and Online Mendelian Inheritance in Man (OMIM)&mdash;had useful numbers of mutations. Comparison of a number of characteristics of these databases indicated substantial inconsistencies between the two databases that included absent genes and missing mutations. This situation strengthens the case for gene specific curation of mutations and the need for an overall plan for collection, curation, storage and release of mutation data.<br /

Sharing data between LSDBs and central repositories.

Several Locus-Specific DataBases (LSDBs) have recently been approached by larger, more general data repositories (including NCBI and UCSC) with the request to share the DNA variant data they have collected. Within the Human Genome Variation Society (HGVS) a document was generated summarizing the issues related to these requests. The document has been circulated in the HGVS/LSDB community and was discussed extensively. Here we summarize these discussions and present the concluded recommendations for LSDB data sharing with central repositories

Go!Poly: A gene-oriented polymorphism database

Human genome polymorphisms play a key role in defining the molecular basis of phenotypic differences between individuals in aspects such as disease susceptibility and drug responses. The database requirements for supporting the study of human genetic variation have been well recognized. In order to meet these needs, several generalized databases have been built. However, it is still hard for users to find gene-related variation data from these huge and sophisticated databases. In its role as a gene-oriented directory of polymorphism data, Go!Poly (Gene Oriented Polymorphism Database; http://61.139.84.5/gopoly/) utilizes two new highly curated and non-redundant resources, LocusLink (http://www.ncbi.nlm.nih.gov/LocusLink/) and RefSeq (http://www.ncbi.nlm.nih.gov/LocusLink/refseq.html), as the standard for identifying and positioning nucleotide variations. As a generalized polymorphism database, Go!Poly extracts human gene-linked sequence variations of all common types (SNP, insertion-deletion, simple tandem repeat, and complex nucleotides variations) from various public resources including scientific journals and internet resources, such as HGBASE (http://hgbase.cgr.ki.se) and dbSNP (http://www.ncbi.nlm.nih.gov/SNP/). The polymorphism data are then categorized into different gene loci, and the reference sequences given by LocusLink are used as positioning references. Through close integration with LocusLink, Go!Poly also provides facilitated connections among sequence data, gene name, and related biological information. This feature also makes Go!Poly easy to search and navigate. Future automated annotations and internal consistency checking may also benefit from this. Extensive efforts are being taken to make the polymorphism information generated by the Chinese scientific community available from this resource

Recommendations for locus-specific databases and their curation.

Expert curation and complete collection of mutations in genes that affect human health is essential for proper genetic healthcare and research. Expert curation is given by the curators of gene-specific mutation databases or locus-specific databases (LSDBs). While there are over 700 such databases, they vary in their content, completeness, time available for curation, and the expertise of the curator. Curation and LSDBs have been discussed, written about, and protocols have been provided for over 10 years, but there have been no formal recommendations for the ideal form of these entities. This work initiates a discussion on this topic to assist future efforts in human genetics. Further discussion is welcome