NEWSLETTERS

NEWSLETTER OF THE
HUGO MUTATION DATABASE INITIATIVE
SPONSORED BY THE MARCH OF DIMES (U.S.A)
No.6 September 1998

INSIDE THIS ISSUE:

MDI ACHIEVEMENTS/PROBLEMS TO BE SOLVED/OBJECTIVES
DENVER MEETING COMING UP
CORRESPONDENCE
- NCBI SNP Database
- IMGT news
ANNOUNCING NEW DATABASES
- HGBASE released
- Prion gene mutations
CALENDAR OF EVENTS
-HUGO MDI Meeting, Denver '98
-Mutation Detection Turin '99

MDI REPORTS ACTIVITIES TO MARCH OF DIMES

A full report outlining the Initiative's achievements and activities was sent to the March of Dimes recently. The main points are summarised below:

Achievements:

ˇ The following major achievements have been made possible by the funds granted from the March of Dimes together with meeting support from HUGO.

ˇ Creation of a consortium of over 400 members in 32 countries.

ˇ Creation of a system of communication via a Website, Newsgroup and Newsletters.

ˇ Initiation of a series of meetings which are held twice per year.

ˇ Encouragement of over 60 locus-specific databases.

ˇ Encouragement of four Ethnic and National databases.

ˇ Spread the word with over 20 talks and posters at least, on Mutation Databases worldwide since October 1996.

ˇ Creation of standards for Nomenclature, Content and Software.

ˇ Initiation of discussion of problematic areas such as Central databases, Copyright and Intellectual property, Patient aspects, Polymorphisms, Ethnic and National databases and Quality Control.

The major problems remaining to be solved include:

1. Uniform data quality for each mutation
2. Rationalization of SNP databases
3. Sustainability via fees for use of database or via advertising on the system
4. Accreditation of databases
5. Naming system for complex mutations
6. Simultaneous searching of all LSDBs
7. Rationalization of Central databases

Our objectives for the next 12 months include:

1. Uniform and agreed entry form for mutations in databases 2. HUGO accredited databases 3. Final recommendations from the current Working Groups 4. Second phase of nomenclature recommendations 5. Final content recommendations 6. Continue canvassing databases 7. Encourage funding for databases via our own funds or from NIH.

DENVER MEETING:

I would like to take the opportunity to remind you all once again that our meeting in Denver -27th October 1998, is coming up. Could those who have not registered please do so as soon as possible. Registration form available at:

http://ariel.ucs.unimelb.edu.au:80/~cotton/register.htm

For more information or copy of the form contact Rania. Sponsorship is invited from those companies interested in mutation databases.

CORRESPONDENCE

NCBI SNP Database

A key aspect of research in genetics is associating sequence variations with heritable phenotypes. The most common variations are single nucleotide polymorphisms (SNPs), which occur approximately once every 100 to 300 bases. Because SNPs are expected to facilitate large-scale association genetics studies, there has recently been great interest in SNP discovery and detection.

At the request of the National Human Genome Research Institute at NIH, and working with them, The National Center for Biotechnology Information has established the dbSNP database to serve as a central repository for both single base nucleotide subsitutions and short deletion and insertion polymorphisms. Once discovered, these polymorphisms could be used by additional laboratories, using the sequence information around the polymorphism and the specific experimental conditions. (Note that dbSNP takes the looser 'variation' definition for SNPs, so there is no requirement or assumption about minimum allele frequency.) The data in dbSNP will be integrated with other NCBI genomic data. As with all NCBI projects, the data in dbSNP will be freely available to the scientific community and made available in a variety of forms.

The database is ready to accept data submissions. DbSNP distinguishes a report of how to assay a SNP from the use of that SNP with individuals and populations. This separation simplifies some issues of data representation. However, these initial reports describing how to assay a SNP will often be accompanied by SNP experiments measuring allele occurence in individuals and populations. Because it is expected that data submissions would typically be done in large batches involving hundreds or thousands of SNPs, a flexible file submission format has been devised. Specification of this format and additional instructions for data submission may be found at:

http://www.ncbi.nlm.nih.gov/SNP/snp.how_to_submit.html

Email questions, etc. to snp-admin@ncbi.nlm.nih.gov

Karl Sirotkin
 NCBI

***

IMGT NEWS

- August 1998 - IMGT, http://imgt.cnusc.fr:8104

"IMGT Scientific Chart - IMGT Repertoire - New Interface"

IMGT, the international ImMunoGeneTics database, announces:

ˇ IMGT Scientific Chart: A description of IMGT standardized rules to ensure the highest quality data (unique numbering, gene name nomenclature, FR-IMGT and CDR-IMGT regions,...)

ˇ IMGT Repertoire: IMGT expertised immunoglobulin and T cell receptor gene tables ("colliers de perles" representations, alignments and tables of alleles, protein displays,...)

ˇ a New IMGT/LIGM-DB interface and eight choices to see results (IMGT annotations, IMGT flat files, coding regions with protein translation, external references,...)

Also new:

- the Mouse (Mus musculus) germline IGKV gene table
- IMGT reference sequences in FASTA format, accessible from IMGT Repertoire and from IMGT/DNAPLOT search page, for downloading

Flash on IMGT:

> 27 000 Ig and TcR sequences of 81 species
> 26 000 sites connected since 1st of January 96
> 4 000 requests a week

IMGT Initiator and coordinator:

Prof. Marie-Paule Lefranc
Laboratoire d'ImmunoGenetique Moleculaire
UPR CNRS 1142, IGH, 141 rue de la Cardonille
34396 Montpellier Cedex 5 - France
Tél. : +33 (0)4 99 61 99 65
Fax : +33 (0)4 99 61 99 01
lefranc@ligm.igh.cnrs.fr

IMGT references :

Lefranc M.-P., Immunology Today, 18, 509 (1997)
Lefranc M.-P., Exp. Clin. Immunogenet., 15, 1-7 (1998)
Pallares N. et al., Exp. Clin. Immunogenet., 15, 8-18 (1998)
Lefranc M.-P. et al., Nucleic Acids Research, 26, 297-303 (1998)

Marie-Paule Lefranc
 Laboratoire d'ImmunoGenetique Moleculaire, LIGM, Montpellier Cedex 5 - France

***

ANNOUNCING NEW DATABASES

HGBASE (Human Genic Bi-Allelic SEquences) database has just been released.

http://hgbase.interactiva.de/

This is a public database of human intra-genic polymorphism designed to contain all types of sequence variations, especially SNPs, found in normal individuals. Many of these polymorphisms are likely to influence phenotypes (e.g. complex disease risk, drug responses) and so it is hoped that HGBASE will provide a useful starting point for the design of association studies and similar analyses.

Contribution of your published and new gene polymorphisms to HGBASE is welcomed and encouraged.

Anthony J. Brookes
Dept. of Genetics & Pathology, Biomedical Center, Uppsala, Sweden

***

Human PRION GENE MUTATION CLASSES

A compilation (updated weekly) and 4,000 pages of articles is now available at:

http://www.mad-cow.org

These include pedigree counts, allowing the frequency of distinct historic occurrences of mutations to be estimated. Japanese language journal coverage is included as are top quality 3D color graphics showing each point mutation on the global NMR structure (when possible) and individual graphics showing a local 3D blow-up of each mutation and brief speculation as to why the change causes CJD, as well as providing local pdb coordinates used for the graphics.

Thomas Pringle
Sperling Foundation, 3295 Kincaid, Eugene, Oregon US 97405

***

CALENDAR OF EVENTS:

-HUGO MDI Meeting, Denver '98
-Mutation Detection Turin '99

***

Hugo Mutation Database Initiative
5th International Meeting
Denver, Colorado, USA, 1998

This meeting will be held the day before the Denver meeting of the American Society of Human Genetics-

TIME: 8.00am-7.00pm
DATE: 27th October 1998
VENUE: Denver Marriot City Centre, Denver Ballroom I/II/III
REGISTRATION:

Academic & Non-Commercial registrants-US$85
Commercial registrants:-US$150
Lunch is included.
ORGANISERS: R. Horaitis, R.G.H. Cotton (Australia)
REGISTRATION:
Contact R. Horaitis
Email: horaitis@ariel.ucs.unimelb.edu.au
Fax: 61-3-9288-2988
Registration form: http://ariel.ucs.unimelb.edu.au:80/~cotton/register.htm

***

HUGO Mutation Detection '99

DATE: 13th -16th May, 1999
VENUE: Turin, Italy.
LOCAL ORGANISERS: -Irma Dianzani, Alberto Ponzone, Clara Camaschella & Alberto Piazza
PRELIMINARY ENQUIRIES TO:

R.G.H. Cotton
Email: cotton@ariel.ucs.unimelb.edu.au
These will then be forwarded to the organisers.