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The HUGO Mutation Database Initiative

The Pharmacogenomics Journal volume 2, pages 16–19 (2002)Cite this article

The human genome has somewhere around 30000 genes.1 If we consider that some genes such as cystic fibrosis have nearly 1000 mutations causing this rare inherited disorder, it is possible that there may be up to 30 × 106 mutations causing single gene disorders if mutations in all genes cause disease. A more conservative figure is 3 × 106. If we consider also non-disease causing polymorphisms that are thought to occur every 200–1000 bases in the 3 × 109 genome, we arrive at 3–15 million possible polymorphisms. In the case of polymorphisms these are important in common disease, in variation in drug metabolism and as markers in linkage studies. When one considers single base changes in the 3 × 109 bases and that each of these can change to one of three others, there are potentially 9 × 109 base changes possible (without insertions or deletions). Thus it is clear that there are likely to be at least tens of millions of base changes that are important to human health. In the case of single gene disorders, each mutational event needs to be characterized by at least 10 extra pieces of data, ideally more like 50,2 whereas polymorphisms perhaps need less. This means that there are at least hundreds of millions of pieces of data that are needed to fully record variation in the human genome. This is only one order of magnitude less than the task of recording the human genome sequence of 3 × 109 units. Thus it is in the interest of medical science that a system be put in place to systematically collect accurate variation data, safely store it, and make it available to those who need the data. It was this impending scenario and a need for a system to cope with it that induced the formation of the HUGO Mutation Database Initiative in 1994. Its history and progress can be seen on its website.3 It has been supported by the Human Genome Organization (HUGO) and the March of Dimes and has around 600 members in 34 countries.

Phenotype variation has been known and used for thousands of years, however molecular variation was only revealed in the 1950s once protein sequencing of mutant proteins was established. The rate of discovery of molecular variation accelerated considerably in the 1960s and 1970s when gene cloning and DNA sequencing were applied to disease genes in rare inherited disorders. The globin gene was perhaps the first human disease gene in which mutations were described. These were collected by those interested in such variation and printed as a book4 and, with the advent of computer databases, were made with relevant software and placed on the WWW. In the case of the globin genes the data from the book have been transferred to a website.5 Also in the 1960s Victor McKusick began collecting inherited syndromes6 and later began listing mutations in the genes that were found mutant and ultimately this listing, online Mendelian Inheritance in Man, has been placed on the Web.7

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  1. Genomic Disorders Research Centre, St Vincent's Hospital Melbourne, Fitzroy, Australia

    R G H Cotton & O Horaitis

  2. Department of Medicine, The University of Melbourne, Melbourne, Australia

    R G H Cotton

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  2. O Horaitis
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on behalf of the HUGO Mutation Database Initiative

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Correspondence to R G H Cotton.

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Cotton, R., Horaitis, O. & on behalf of the HUGO Mutation Database Initiative. The HUGO Mutation Database Initiative. Pharmacogenomics J 2, 16–19 (2002). https://doi.org/10.1038/sj.tpj.6500070

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