Human Gene Mutation Database?A biomedical information and research resource

Abstract

Although 20 years have elapsed since the first single basepair substitution underlying an inherited disease in humans was characterised at the DNA level, the initiative has only recently been taken to establish central database resources for pathological genetic variants. Disease-associated gene lesions are currently collected and publicised by the Human Gene Mutation Database (HGMD) in Cardiff, locus-specific mutation databases, and to some extent also by the Genome Database (GDB) and Online Mendelian Inheritance in Man (OMIM). To date, HGMD represents the only comprehensive and publicly available database of gene lesions underlying human inherited disease. By July 1999, HGMD contained over 18,000 different mutations from some 900 human genes, the majority being single basepair substitutions. In addition to its potential as an information resource for clinicians and genetic counsellors, HGMD has allowed molecular geneticists to address a variety of biological questions through meta-analysis of the collated data. HGMD also promises to assist research workers in optimising mutation search strategies for a given gene. A questionnaire sent out to, and answered by, the editors of 20 key journals revealed that human genetics journals are increasingly reluctant to publish mutation reports. Electronic data submission and publication facilities are therefore urgently required. The World Wide Web (WWW) provides an excellent medium within which to combine the centralised management of basic mutation data, including rigorous quality control, with the possibility of publishing additional mutation-related information. In response to these needs, HGMD has both instituted a collaboration with Springer-Verlag GmbH, Heidelberg, to potentiate free online submission and electronic publication of human gene mutation data and developed links with the curators of locus-specific mutation databases.

Interleukin-1 Receptor-associated Kinase-2 Genetic Variant rs708035 Increases NF-κB Activity through Promoting TRAF6 Ubiquitination

“…Some SNPs have been proven to be very important and may be associated with human diseases. SNPs that lead to amino acid alteration in the protein are of particular interest because they are responsible for nearly half of the known genetic variations related to human inherited diseases (42). Researchers have found that some SNPs could change the response of an individual to certain drugs, susceptibility to environmental factors, such as microbial, and risk of developing particular diseases.…”

Dobzhansky–Muller incompatibilities in protein evolution

“…3). Indeed, F must approach zero (or nearly so) when we consider organisms that are increasingly close to humans, because suppressor (compensatory) substitutions rarely segregate in human populations, and most mutations causing Mendelian diseases are pathogenic unconditionally (26). Almost certainly, a mutation that is pathogenic to us was also pathogenic to Neanderthals.…”

Association Rule Mining in Genomics

“…All HGMD entries comprise a reference to the first literature report of a mutation, the associated disease state as specified in this report, the gene name, symbol and chromosomal location [11].…”