Michael Krawczak, Edward V. Ball, Peter Stenson, Iain Fenton, David N. Cooper
Institute of Medical Genetics, University of Wales College of Medicine
Heath Park, Cardiff CF4 4XN, UK,
Phone: (+44) 1222 744062 (DNC) or (+44) 1222 744957 (MK), Fax: (+44) 1222 747603
cooperdn@cardiff.ac.uk or krawczak@cardiff.ac.uk
The Human Gene Mutation Database (HGMD), maintained at the Institute of Medical Genetics in Cardiff, represents a comprehensive core collection of data on published germline mutations in nuclear genes underlying human inherited disease. By August 1998, the database contained in excess of 14,300 different lesions in a total of 783 different genes, with new entries currently accumulating at a rate of over 2,500 per annum. Although originally established for the scientific study of mutational mechanisms in human genes, HGMD has acquired a much broader utility in that it provides information of practical importance to researchers in human molecular genetics, physicians interested in a particular inherited condition in a given patient or family, and genetic counsellors. Furthermore, integration with phenotypic, structural and mapping information has been accomplished through bi-directional links between HGMD and both the Genome Database (GDB) and Online Mendelian Inheritance in Man (OMIM), Baltimore, USA. In view of its potential usefulness, the curators of HGMD made the database publicly available via the Internet1 in April 1996. HGMD currently serves in excess of 200,000 search requests per annum. Mutation data in HGMD are accessible on the basis of every gene being allocated one Internet page per mutation type, if data of that type are present. Mutation maps of every gene provide a graphical display of mutations within the coding regions so that the distribution of such lesions can be assessed at a glance. Summary data on the frequencies of different types of amino acid substitutions, the location of splicing relevant single base-pair substitutions and the sizes of micro-deletions and insertions in HGMD are also presented. The links to GDB and OMIM have enforced the standardisation of disease and gene nomenclature in HGMD. Thus HGMD can be searched either by HUGO-approved gene symbols, GDB accession numbers, or OMIM-compatible disease or gene names. For genes for which Locus-Specific Mutation Databases are available on the Internet, these databases can be accessed either from the corresponding gene-specific HGMD pages or via the Locus-Specific Mutation Database page2.
Data acquisition for HGMD has been accomplished by a combination of manual and computerised search procedures, scanning in excess of 250 journals on a weekly/monthly basis. Coverage is limited to original published reports although some data are taken from review articles. The curators of HGMD have adopted a policy of entering each mutation only once since information necessary for reliable discrimination between recurrency and identity-by-descent is available only for a very small proportion of known lesions.
Looking to the future, efforts will be made to improve the provision of flanking sequence data, to increase the number of cDNA and genomic reference sequences provided, and to make the data collections on gross gene lesions and disease-relevant polymorphisms fully comprehensive. In order to improve the accuracy, efficiency and rapidity of mutation publication, however, direct submission of mutation data to a central resource capable of (and responsible for) checking the novelty and consistency of data is both necessary and desirable. To this end, HGMD has instituted a collaboration with Springer-Verlag GmbH, Heidelberg, to make online submission and electronic publication of human gene mutation data possible3. These data are being published regularly by Springer in its journal Human Genetics and subsequently transmitted to Cardiff to be deposited in HGMD.
Internet Addresses
1.
http://www.uwcm.ac.uk/uwcm/mg/hgmd0.html
2.
http://www.uwcm.ac.uk/uwcm/mg/oth_mut.html
3.
http://link.springer.de/journals/humangen/mutation
Acknowledgements
The curators of HGMD are grateful for the financial support of SmithKline Beecham, Pfizer, the Genome Database and the Deutsche Forschungsgemeinschaft.
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