Time for a Unified System of Mutation Description and Reporting: A Review of Locus-Specific Mutation Databases

Abstract

Mutation databases of human genes are assuming an increasing importance in all areas of health care. In addition, more and more experts in the mutations and diseases of particular genes are curating published and unpublished mutations in locus-specific databases (LSDB). These databases contain such extensive information that they have become known as knowledge bases. We analyzed these databases and their content between June 21, 2001, and July 18, 2001. We were able to access 94 independent websites devoted to the documentation of mutation containing 262 LSDBs for study. We analyzed one LSDB from each of these websites (i.e., 94 LSDBs) for the presence or absence of 80 content criteria, as generally each gene in a multigene website documented the same criteria. No criterion studied gave unanimous agreement in every database. Twenty-two genes were represented by more than one LSDB. The number of mutations recorded, excluding p53, was 23,822 with 1518 polymorphisms. Fifty-four percent of the LSDBs studied were easy to use and 11% hard to follow; 73% of the databases were displayed through HTML. Three databases were found that were given a high score for ease of use and wealth of content. Thus, the study provided a strong case for uniformity of data to make the content maximally useful. In this direction, a hypothetical content for an ideal LSDB was derived. We also derived a community structure that would enhance the chances of mutation capture rather than being left unpublished in a patient's report. We hope the interested community and granting bodies will assist in achieving the vision of a public system that collects and displays all variants discovered.

The Moroccan Genetic Disease Database (MGDD): a database for DNA variations related to inherited disorders and disease susceptibility

“…2,3 LSDBs are generally developed and maintained by experts with particular interest to a single gene or chromosomal locus. 4 NEMDBs record mutation spectrum observed in a particular population or ethnic group; they provide relevant information to study the population origin and migration flow. 5 The Human Genome Variation Society (HGVS) maintains comprehensive and updated lists of LSDBs and NEMDBs, in a dedicated website (http://www.hgvs.org), which presents guidelines and recommendations to generate the content and structure of variation databases.…”

Recommendations for locus-specific databases and their curation

“…This list must be close to the ideal content and was therefore used as a basis for recommendations [Claustres et al, 2002;Horaitis and Cotton, 1999(updated in 2003]. The variant submission form suggestion reflected this content [Horaitis and Cotton, 1999] Table 1), although priority was given to any information that was considered to be crucial.…”

“…The review of Claustres et al [2002] examined 100 representative LSDBs and found 80 characteristics that the curators had included. This list must be close to the ideal content and was therefore used as a basis for recommendations [Claustres et al, 2002;Horaitis and Cotton, 1999(updated in 2003].…”

“…Finally, collections of LSDBs are emerging that use one software tool and run on a single server, but each is curated by an expert [Beroud et al, 2000;Fokkema et al, 2005]. The software for creating these LSDB collections reflect the defined characteristics obtained by the survey of Claustres et al [2002] and is freely available (LOVD and UMD; see Table 1). The software used for the Immunogenetics database on a single server uses a third software [Riikonen and Vihinen, 1999] (see Table 1).…”

“…There have been many publications on LSDBs, including a review of content and recommendations for essential data fields [Claustres et al, 2002], recommendations for setting up an LSDB [Horaitis and Cotton, 1999] (updated in 2003 and 2005), recommendations for submission forms [Horaitis and Cotton, 1999] (see also form by A.D. Auerbach et al at www.hgvs.org/ entry.html, and Table 1) and listings of LSDBs [Horaitis et al, 2007]. However, despite all this, and despite the existence of almost 700 databases that we refer to as LSDBs, there has been neither an agreed definition of the ideal LSDB nor a definition of how they should be curated.…”