Human Variome Project Coordinating Centre

This core function is critical to the success of the project as it is to collect and connect globally all projects/workers interested in collection of mutation so that efficiencies are promoted in the quest for collection of all legacy data and construction of pipelines. This will enable effortless transmission of patient phenotype and genotype via expert curation and locus specific databases (LSDBs) to central browsers at NCBI, EBI and UCSC Genome Browser. Also a centre function will be the integration of standards into the global collection systems, for example: prerequisite for reporting from diagnostic laboratories to comply with licensing.

Contact: R. Cotton ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it ) Melbourne, Australia.

HVP/InSiGHT Pilot Project with four colon cancer genes

The long established and international group (http://www.insight-group.org) has, in collecting data for its own use in clinics and research, volunteered to be a pilot for collecting data for all genes for all countries. Thus the world’s expertise is being drawn on to establish this system which is well underway. This system is intended to form the template for other disease/specific gene collections, other groups presently interested are those interested in a database mutation causing “Neurological” disease and the Nutrigenomics group NUGO

Contact: F. Macrae ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it ) Melbourne, Australia.

Pilot collection from individual countries

For collection of mutation to be complete, collection has to be on a country by country basis for all genes and it would be ideal if this was part of best practice/QA/laboratory licensing (see below). UK has initiated this on a custom made database (DMuDB; http://ngrl.man.ac.uk/dmudb/index.html). The InSiGHT group (above) will pilot country specific collection for four genes worldwide. Australia is now in the process of setting up a pilot system to create a country specific data collection system and database. To assist this effort Laboratories in Queensland have decided to start collecting their data with the use of LOVD software (Drs. Hyland, McMillan and Jones). The pilot system created in Australia will form a template for other countries. The HVP intends to establish an International Consortium of Countries to further assist in the establishment of country specific databases.

Contact: R. Cotton ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it ) Melbourne, Australia.V. Hyland ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it ) Brisbane, Australia; Heather Howard ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it ) Melbourne, Australia

Establishment of global collection of mutation

Most diagnostic labs/clinical genetics/genetic counsellors attempt to search the available global collection of mutations on a daily basis. Thus they would help themselves if all discoverers of variations placed their mutations and phenotype on the web. They know this, thus the worldwide support of the project and specifically the driven and passionate activity of InSiGHT, the inherited colon cancer group. The project can be simplified by models, pilot studies, protocols spreading the loads and various incentives. Much of this is underway as discussed above. Contact with numerous countries has already occurred and access to all is not complicated. At the 2006 HVP meeting 20 countries were represented and a further 10 were represented and 1 contributed but did not attend the HVP Planning Meeting in 2008. Both our journal Human Mutation and Nature Genetics are collaborating to encourage a new type of Mutation Update (an original feature of Human Mutation) whereby the author contacts all labs known to be describing mutations in a particular gene. They will submit their mutations and the publication with the mutations will have the submitters as an author. R. Cotton has reached all Gulf countries by speaking 3 times in the area and has been invited twice to Korea once to initiate the Korean Variome Project. He has spoken at around 20 international meetings on the project (see below). His task is to inform and pursue those who have data to contribute, who need data, and inform them of the latest relevant developments to inform their actions. The HVP intends to establish an International Consortium of Countries to further assist in the establishment of country specific databases and universal nomenclature and standardisation. A meeting on this topic is planned.

Contact: R. Cotton ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it ) Melbourne, Australia.

Pathogenicity of unclassified variants (UVs)

Enormous amounts of time is wasted to see if a missense variant (in particular) has been found around the world to inform a specific patient being counselled. Independently Dr. Tavtigian called an IARC meeting in February 2008 in Lyon dealing with BRCA. We managed to have key InSiGHT individuals including (Dr. Genuardi and Greenblatt) attend and also to have them publish eight papers in our journal Human Mutation. A formal committee is carrying this forward with many world experts since the HVP Planning Meeting in 2008.

Contacts: M. Genuardi ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it ) Florence, Italy; S. Tavtigian ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it ) Lyon, France; M. Greenblatt ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it ) Burlington, U.S.A.

Input to Central Databases of mutation data

Central databases such as NCBI and EBI had until several years ago been focused on SNP data generated by massive and well-funded sequencing efforts. The PhenCode project started placing LSDBs on the UCSC Genome Browser a few years ago. After the meeting in Melbourne to initiate the HVP there were two NCBI staff members in attendance and it became clear that they wished to include LSDB. Sue Povey led the way with her TSC2 database as a direct consequence of one of the 96 recommendations of the HVP Melbourne meeting (Nat Genet 39(4): 433-6, 2007). The HVP Planning Meeting ensured contact between the “HVP/InSiGHT Pilot” (see above), the InSiGHT collaborators and NCBI and EBI scientists and the UCSC collaborators and plans are being developed to place the InSiGHT databases on these two major databases. A document concerning which data to share has recently been developed by HVP/HGVS members and published in Human Mutation.

Contact: D. Maglott ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it ) Baltimore, U.S.A.; P. Flicek ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it ) Cambridge, U.K.; F. Macrae ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it ) Melbourne, Australia.

Microattribution for variations, etc

Myles Axton conceived this after attending the 2006 HVP meeting (see Nat Genet 40(1): 1, 2008). In this scheme whilst there will not be a publication but references to data will be counted and hence a value can be put on it.

Contact: M. Axton ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it ) New York, U.S.A.

Adopt a Gene

Curation of gene specific collections of mutations are essential, not only to collect them, but also to ensure they are correct as 5, 10 and 43% of literature reports were found to be incorrect by 3 curators of different genes. No central body could afford to pay a curator for each of the 2,000 genes at between $1,000-$100,000 per year. The Adopt a Gene scheme was developed to spread the cost of this load with adopters paying say $10,000 per year in return for their logo on the LSDB website and the company can announce this on their website. This strategy was approved by Francis Collins and The Wellcome Trust. CMO-Global is the first company curating the genes for Paola Carrera for her Familial Hemiplegic Migraine database (http://grenada.lumc.nl/LOVD2/FHM/home.php).

Contact: R. Cotton ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it ) Melbourne, Australia.

Effective text processing and search techniques

LSDB curators, clinicians and diagnosticians need to access published material with a minimum of effort. Some protocols are available but are not ideally suited to searching for DNA mutations. Tim Smith (GDRC) is doing a PhD on this topic and a NICTA staff member is available under the supervision of Dr. Cavedon. Thus development of appropriate text mining and biomedical retrieval strategies are under development.

Contact: L. Cavedon ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it ) Melbourne, Australia.