7 September 2006

Dear Editor,


I recently was given the opportunity to attend the Human Variome Project Meeting ( in Melbourne, convened by Professor Richard Cotton, AM, director of the Genomic Disorders Research Centre and president of the Human Genome Variation Society (

The HGVS (previously the Human Genome Organisation – Mutation Database Initiative) was established in 1994. It has been instrumental in establishing guidelines for universal nomenclature for DNA sequence variants, promoting uniform informatics systems to allow sharing of information, setting minimum standards for all genetic databases and bringing together leading international researchers for this much needed working group1 (see

Present were 50 speakers from peak Genetics bodies worldwide and 20 observers from three key fields, including laboratory and molecular genetics, clinical genetics and bioinformatics. Also present were representatives from government agencies, the World Health Organization, The American College of Medical Genetics, a dozen Genetics journals, Google and philanthropic and funding agencies such as the March of Dimes and the EC to list a few. More than 20 countries were represented (see for details).

Broadly speaking, this important international project aims to foster the documentation of variation identified within the human genome paired with associated phenotypic information, to ensure that good quality information is freely accessible to researchers, clinicians and patients. The purpose is several fold:

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    To improve understanding of the pathophysiology of genetic disease and how genetic variation contributes to disease risk
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    To document the frequency of specific sequence variations within populations
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    To improve diagnostic methods, treatments, genetic counseling and understanding of the clinical trajectory for patients harboring specific sequence alterations
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    Ultimately to benefit the health of all humans

This follows the Human Genome Project which was initially thought an impossible undertaking. However, in June 2000 the first draft sequence was complete, with >90% of the three billion base pairs determined2,3 at a cost of $2.7 billion US dollars (see The technical advances made over the course of that project meant completion was years earlier than predicted and the project was significantly under budget. However, by its very nature, any project that seeks to document human genetic variation will never be ‘complete’.

Despite the enormous difficulties present in tackling this mammoth task, and the differing focus of each group present, the mood was overwhelmingly positive. Several key agreements were reached, including:

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    To seek large-scale funding support from various governments
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    To encourage gene experts to perform database curation
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    To facilitate the inclusion of ‘dollar poor’ countries many of which were unable to contribute to the Human Genome Project but without whose participation the Human Variome Project will be incomplete
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    To identify and promote debate around the numerous ethical implications of the project
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    To coordinate the project from the GDRC in Melbourne

The outcomes of the meeting and the future work of this group will have wide-reaching implications and will increasingly influence the practice of all clinicians.4,5 With free public access to an electronic resource that allows searching at the level of DNA sequence, specific gene, protein structure or function, phenotype (both at a cellular and a whole organism level) and even physical symptoms and signs, clinicians from all disciplines will be confronted with this either through their own initiative or through that of the families for whom they are providing care.

If the outcome of the Human Genome Project is to mean anything to clinicians other than a string of letters, this next phase of accurately documenting genetic variation and phenotypic correlates is vital. While technological advances facilitated the early completion of the Human Genome Project, it is unlikely that a similar circumstance will apply to documenting human genetic variation and its significance. The key challenge as we look further into this new millennium will be to apply meaning to that variation, and to ensure that the information is quality controlled and readily accessible to all. This task requires expert clinical judgment, and the cooperation and collaboration of human beings from all fields, perhaps most importantly the patients themselves.


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  1. Dr Brown attended the Human Variome Project Meeting as an invited observer financially supported by the Victorian State Government.