HUGO Mutation Database Initiative Meeting

Edinburgh, Scotland

19 April 2001

Meeting Report - full version - Reported by Saeed A. Teebi

Posted 29th June 2001

Invited Abstracts

Saeed Teebi - BiSC WayStation and Central Database: Prototype 2
Tony Brooks and Heikki Lehvaslaiho - HGBASE - A Unified Human SNP Database
Maryam Neishabury - Iranian Human Mutation Gene Bank
Julia Ponomarenko - rSNP_Guide; a database system for studying transcription factor binding site altered by genome mutation
Nobuyoshi Shimizu - MutationView Update


.Human Mutation as the Official Journal of MDI
.MDI as an Official Society
.Funding Questions

Invited Abstracts

The 10th International HUGO-Mutation Database Initiative Meeting was chaired by Richard Cotton and Arleen Auerbach on 19 April 2001. It was made up of two segments, a Scientific Meeting and a Business Meeting. For each segment, formal presentations were made, each followed by an open discussion. Forty registrants attended the meeting.

Saeed Teebi of the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Canada, began the Scientific meeting by presenting the BiSC WayStation and Central Database, both in their 2nd prototype of development. The WayStation is a web-accessible, streamlined system designed to accept, at a central point, novel allelic variation data from researchers worldwide, subject them to expert review and ultimately retransfer them to appropriate databases where they can be stored and made publicly available. The WayStation's Review Board is composed of the curators of locus-specific databases (LSDBs) as well as orphan gene editors.

A proposed scheme, still under discussion, would allow submissions to the WayStation to be granted a PubMed ID, accompanied by a HuMu ID from the journal Human Mutation; this would act as both a record and proof of a valid submission. As well, the granting of PubMed IDs to researchers would act as an incentive to submit to the WayStation. It is still unresolved what kinds of submissions would be eligible to receive a PubMed ID (see discussion below).

The BiSC Central Database Pilot that holds WayStation submissions and the data of selected LSDBs was also presented. The number of LSDBs archived in the Pilot has reached 23, covering 30 loci.

Significantly, both the WayStation and Central Database are now operational and ready for the installation of a Review Board to begin accepting submissions. However, it was stressed that they are also "bare-bones" structures; further development is strongly desirable and requires funding. Operational demonstrations of the WayStation and Central Database may be accessed at

Tony Brookes of the Karolinska Institute, in Sweden, and Heikki Lehväslaiho of EBI in the UK, took the podium next and spoke jointly about HGBASE, a catalogue of human SNPs [Brookes et al., 2000; Sarkar et al., 1998]. The data in HGBASE is as comprehensive and non-redundant as possible, harvested from public databases, published literature and individual solicitations of and submissions from scientists. To accumulate as much data as possible, HGBASE tries to adapt to the submission capabilities and desires of its users. Importantly, whatever data entered into HGBASE data automatically becomes part of the public domain. The focus in HGBASE is on genes and increased annotation; it is highly curated as the data is subjected to both automatic checking (e.g. EBI's Mutation Checker software) and manual review.

HGBASE data is also included in the graphical genome representation project ENSEMBLE, which aims at eventually covering all protein-coding genes. Core data exchange with dbSNP was initiated last year.

HGBASE is available free of charge at Proprietary companies like Celera are allowed to carry HGBASE data on their web sites, but, as a matter of principle, are not allowed any kind of exclusivity. They are also subjected to certain guidelines such as showing the whole database, having links to the source data location, etc. Release 9 of HGBASE, documenting >1 million SNPs, is slated for 2001.

The Iranian Mutation Gene Bank was presented by Maryam Neishabury from the University of Welfare and Rehabilitation in Tehran. Iran is a large country of 66 million, a population that is highly heterogeneous genetically because of its geography (mountains and deserts), history (foreign invasion and bi-directional immigration) and culture (consanguineous marriages). The diversity in the gene pool is reflected in the high number of new and rare disorders. With the primary aims of improving diagnostics and determining common mutations, the Gene Bank stores the DNA of patients in Iran with genetic diseases, as well as that of their first-degree relatives. The clinical profile of the patients as well as a DNA sample and a comprehensive pedigree are examples of what is contained in the Bank.

The Bank can be used as a study tool, a diagnostic aid, a method to determine common mutations and as a link for patients to support groups. The Gene Bank is accessible at and offers a resource of samples to researchers worldwide.

Julia Ponomarenko of the Institute of Cytology and Genetics in Russia presented rSNP_Guide, a database system with natural and artificial mutation data for discovering transcription factor (TF) sites, whose presence in mutated regulatory sites explains susceptibility to disease [Ponomarenko et al., 2001]. rSNP_Guide contains four cross-linked sub-databases: 1) rSNP_DB, storing data describing the effect of a regulatory region SNP on interaction with nuclear proteins; 2) rSNP_BIB, which accumulates the references to original publications; 3) SYSTEM, storing experimental results; and, 4) rSNP_Report, storing the protocols of predictions that are confirmed experimentally. The rSNP_Guide web site is available at

Finally, Nobuyoshi Shimizu of the Keio University School of Medicine in Japan gave an update on the MutationView variation viewing software [Minoshima et al., 2001]. Currently MutationView is implemented on various independent databases, covering 175 genes and, at last count, 4614 variations. There have been several improvements, including increased graphical entry windows for the human anatomy and improved viewing and sorting methods.

Soon to be renamed as VariationView, MutationView is accessed using a user name and password scheme that is free to those who demand it. MutationView and its subsidiary databases can be found at


Mark Paalman, Managing Editor of Human Mutation opened the Business meeting with a discussion of the previously accepted idea of adopting the publication as the official journal of the MDI (at the MDI meeting in Philadelphia, Oct. 2000). He outlined three benefits: 1) increased Society awareness, as HuMu would be promoted as the "official journal of HUGO-MDI"; 2) greater potential revenue streams and publication discounts; and, 3) facilitation of the process of getting a HuMu ID/PubMed ID granted to a WayStation submission. He also introduced the term "Gene Variation Report" (GVR), the successor to the Mutation and Polymorphism Report (MPR) formerly published in HuMu. GVRs, which are generated by submission to and review through the WayStation, would be candidates for the granting of PubMed IDs/HuMu IDs.

An open discussion ensued, revolving around the many unresolved issues that arise in such a scenario. Some of the salient questions were:

. what constitutes a unit of publication?
. what data the user would see in a PubMed record when each variation submission is given an ID?
. would there be an electronic publication or some other permanent, public structure to document these certified submissions?
. is HuMu's assistance is needed to interact with NLM in the first place?

It was agreed that the main reasons for granting a PubMed ID to WayStation submissions would be to: a) ensure a reasonable review of the submission has occurred, and b) keep an archive of reported and reviewed variations. The remaining questions are of specific nature will have to be discussed at length and eventually settled at later meetings and over the MDI mailing list. A consensus to adopt HuMu as the official journal of the MDI was confirmed.

Richard Cotton then reintroduced the question of making the MDI into an official Society, since one is needed to have the capacity to sign any agreement with Wiley-Liss, the publisher of HuMu. A consensus was reached to do so. Also, a mandatory subscription to HuMu was discussed as a good co-requisite for MDI membership. Thus, the action items for the MDI's leadership became:

1. Obtaining legal advice towards the formation of a Society
2. Undertaking to obtain nominations for positions in the newly-formed Society with binding signatory powers
3. Voting on President and other office-holders
4. Signing the Wiley-Liss agreement to make HuMu the official journal of the Society

It was agreed that all these goals should be accomplished by 15 June 2001.

The question of funding for the WayStation was the focus of the last discussion of the day. It was acknowledged that the Incyte venture, which had seemed like a promising source of collaboration on a federated variation database, had failed. Funding was still very important, and other options were discussed. Arleen Auerbach focused the discussion on generating an application for funding to the NIH, especially since NIH sources had explicitly encouraged such an application [Auerbach, 2000]. She stated that a collaborative project was especially favourable, with the Principal Investigator acting as a subcontractor to the other collaborating parties. The importance of incorporating some of the major extant databases (e.g. HGBASE) into the application was stressed. Such a database would work well with the WayStation in acting as a warehouse for submissions.

In addition, it was agreed that the corporate route to funding should not be abandoned, and to that end, several potential private-party backers were discussed. Some of the companies that could potentially be interested in supporting this initiative in the future are Informax and DoubleTwist.


Auerbach AD. 8th International HUGO-Mutation Database Initiative Meeting, April 9, 2000, Vancouver, Canada, 2000, Hum Mutat 16:265-268.

Brookes AJ, Lehväslaiho H, Siegfried M, Boehm JG, Yuan YP, Sarkar CM, Bork P, Ortigao F. HGBASE: a database of SNPs and other variations in and around human genes Nucleic Acids Research, 2000, Vol. 28, No. 1 356-360.

Minoshima S, Mitsuyama S, Ohtsubo M, Kawamura T, Ito S, Shibamoto S, Ito F, Shimizu N. The KMDB/MutationView: a mutation database for human disease genes. Nucleic Acids Res. 2001 Jan 1;29(1):327-8.

Ponomarenko JV, Merkulova TI, Vasiliev GV, Levashova ZB, Orlova GV, Lavryushev SV, Fokin ON, Ponomarenko MP, Frolov AS, Sarai A. rSNP_Guide, a database system for analysis of transcription factor binding to target sequences: application to SNPs and site-directed mutations. Nucleic Acids Research, 2001, Vol. 29, No. 1 312-316.

Sarkar C, Ortigao FR, Gyllensten U, Brookes AJ. Human genetic bi-allelic sequences (HGBASE), a database of intra-genic polymorphisms. Mem Inst Oswaldo Cruz 1998 Sep-Oct;93(5):693-4


Copyright HUGO MDI 2000 Created by Rania Horaitis Posted 29th June 2001
Coordinator Rania Horaitis