The Human Variome Project (HVP) 2009 Forum "Towards Establishing Standards".

The May 2009 Human Variome Project (HVP) Forum "Towards Establishing Standards" was a round table discussion attended by delegates from groups representing international efforts aimed at standardizing several aspects of the HVP: mutation nomenclature, description and annotation, clinical ontology, means to better characterize unclassified variants (UVs), and methods to capture mutations from diagnostic laboratories for broader distribution to the medical genetics research community. Methods for researchers to receive credit for their effort at mutation detection were also discussed.

A survey of locus-specific database curation. Human Genome Variation Society.

It is widely accepted that curation of variation in genes is best performed by experts in those genes and their variation. However, obtaining funding for such variation is difficult even though up-to-date lists of variations in genes are essential for optimum delivery of genetic healthcare and for medical research. This study was undertaken to gather information on gene-specific databases (locus-specific databases) in an effort to understand their functioning, funding and needs. A questionnaire was sent to 125 curators and we received 47 responses. Individuals performed curation of up to 69 genes. The time curators spent curating was extremely variable. This ranged from 0 h per week up to 5 curators spending over 4 h per week. The funding required ranged from US$600 to US$45,000 per year. Most databases were stimulated by the Human Genome Organization-Mutation Database Initiative and used their guidelines. Many databases reported unpublished mutations, with all but one respondent reporting errors in the literature. Of the 13 who reported hit rates, 9 reported over 52,000 hits per year. On the basis of this, five recommendations were made to improve the curation of variation information, particularly that of mutations causing single-gene disorder: 1. A curator for each gene, who is an expert in it, should be identified or nominated. 2. Curation at a minimum of 2 h per week at US$2000 per gene per year should be encouraged. 3. Guidelines and custom software use should be encouraged to facilitate easy setup and curation. 4. Hits per week on the website should be recorded to allow the importance of the site to be illustrated for grant-giving purposes. 5. Published protocols should be followed in the establishment of locus-specific databases.

The challenge of documenting mutation across the genome: the human genome variation society approach.

New methods for the detection of mutations and the completion of the human genome sequencing project have contributed to an exponential rise in variation information that must be collected, quality controlled, documented, and stored safely to ensure future availability to health care professionals, researchers, and others. There may be anywhere from one to more than 1,000 mutations in any given gene. To date, this information has been collected by general databases such as Online Mendelian Inheritance in Man (OMIM) or the Human Gene Mutation Database (HGMD), which collect only published mutations and, in the case of OMIM, selected published mutations. Unpublished mutations have made their way into Locus Specific Databases (LSDBs), and these can often contain as many unpublished mutations as published ones, in addition to other more detailed gene-specific information. LSDBs, however, do not exist for all genes at this time. Through their interactions, a number of members of the Human Genome Variation Society (HGVS) have developed nomenclature, standard software to curate mutations in gene specific databases, a WayStation to collect and review new mutations from research and diagnostic laboratories, and central databases to store and display these mutations and their associated phenotypes. Nomenclature is now well defined for the commonest types of mutation, with work continuing on systematically naming the more complex types. Other projects, such as dedicated specialized software for LSDBs, are in the early stages of development.

Human mutation databases.

The first part of this unit compares general and locus-specific mutation databases. The second section deals with submitting data. The third part provides guidance for accessing mutation data. The final section offers advice on database construction.

Human mutation databases.

The first part of this unit compares general and locus-specific mutation databases. The second section deals with submitting data. The third part provides guidance for accessing mutation data. The final section offers advice on database construction.

Time for a unified system of mutation description and reporting: a review of locus-specific mutation databases.

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.