A growing urgency to change

17 Nov 2011

According to Johan den Dunnen there are no valid reasons for not publishing all data on gene variants in a public database. "We urgently need access to this information, otherwise it is useless to perform whole genome analysis."

For a long time already, multiple efforts are ongoing to make all discovered gene variants accessible through public databases. So far, progress has been very limited and there is still no easily accessible, internationally accepted database that brings all the information (gene variants, phenotype descriptions, clinical information) together. "Currently, the vast majority of gene variants are not published at all. Academic and commercial diagnostic labs, as well as most researchers don't bother to make their findings available to the community", says den Dunnen, professor of Medical Genome Technology at the Leiden University Medical Centre. Discussions on the need for a standardized, curated and publicly accessible database have been going on for a long time, but the advent of whole genome sequencing in routine clinical practice is creating a sense of urgency. Den Dunnen: "The extent of the problem is dawning quickly. You can deal with three variants in the conventional manner of analysis, but confronted with a list of 10,000 variants or more, you are nowhere if you don't have access to a central resource for retrieval of relevant information. Using modern sequencing technology, clinical geneticists and diagnostic labs are confronted with such lists. The urgency is high and will only increase because physicians and patients will want the results on short notice."

MutaDATABASE
One of the initiatives that aim to come to a manageable and sustainable solution is MutaDATABASE (www.mutadatabase.org), in which den Dunnen is a participant. A correspondence by the MutaDATABASE consortium in Nature Biotechnology earlier this year (Feb 2011) led to a discussion with other initiatives in the field, including the Human Variome project and the Gen2Phen consortium. Den Dunnen emphasizes that he also participates in those initiatives and remains neutral on the back-and-forth comments that have been published in Nature Biotechnology (links listed below). "I am basically part of both sides in this discussion. This type of quarrelling usually comes up when an opportunity for funding is appearing. To me, the most important thing is that we are going to act. These discussions have been going on far too long already. We could have prevented this whole situation if we would have started acting ten years ago. It was clear that the technology was developing in this direction."

Compulsory
What is the crucial factor for this to become a success? How can you ensure that researchers will submit their data? Den Dunnen: "After many years I see only one solution, which is that it should be compulsory for anyone who performs such an analysis to submit the result and the accompanying clinical information in a public database and it should be obligatory to consult this database to interpret your results and formulate conclusions for the patient and physician." He does not share the much-heard concerns on privacy issues relating to such sensitive information. "Physicians are bound to act in the best interest of their patients and to me it is clear that having access to this information and thus sharing information is in the best interest of the patient. When nobody shares we can stop using DNA diagnostics because we have nothing to refer to. Many researchers and physicians use the need to be careful as an excuse, but this is really stalling the process. With the right software, all these concerns can easily be addressed." He has been around long enough that it will take a lot of time and effort to establish a new routine. But he stresses that there is no alternative. "If we don't make this work, the progress in sequencing technology has been in vain. Performing whole genome analysis is useless without access to this type of information. On the upside, if we have the funds and the will to change, we can make it happen in less than a year."

For the discussion in Nature Biotechnology, check

Bale et al.
MutaDATABASE: a centralized and standardized DNA variation database
Nature Biotechnology 29 117-118 (2011) (original correspondence)

Dalgleish et al.
Clarity and claims in variation/mutation databasing
Nature Biotechnology 29 790-792 (2011) (comment)

Bale et al.,
Reply to clarity and claims in variation/mutation databasing
Nature Biotechnology 29 792-794 (2011) (reply)

For related correspondence by members of the International Scientific Advisory Committee of the Human Variome Project (including Johan den Dunnen)
Mutation (variation) databases and registries: a rationale for coordination of efforts
Nature Reviews Genetics, doi:10.1038/nrg3011-c1 (published online 25 October 2011)