Mutation Database Meeting
27th March 1998
Lingotto Conference Centre
A. Coordination of Mutation Databases - Working Group Report.
Reported by Richard G.H. Cotton
- March of Dimes is paying the salary for one person in Melbourne to work on Coordination of the initiative, including Newsletters and identifying and encouraging new databases and working groups.
- There are now ~400 people on the mailing list.
- There are now a number of websites such as EBI, Cardiff database and many locus specific databases. Many groups encouraged to create a database are now working on this.
B. Nomenclature Working Group Report.
- Stylianos Antonarakis was not present at the meeting due to illness, but the meeting was informed that there is now a published nomenclature agreement - S.Antonarakis and the Nomenclature Working Group: Recommendations for a Nomenclature System for Human Gene Mutations. Hum Mutat 11:1-3 (1998). The group will continue to enlarge and modify this agreed nomenclature and work towards the problem of naming complex mutations.
C. Content and Software Working Group Report
Reported by Charles Scriver
- A draft of a document "Guidelines and Recommendations for Content and Structure of Mutation Databases" authored by Scriver, Nowacki et al. is available on the web at:
This includes an appendix adapted from a web document created by Heikki Lehvaslaiho (EBI). Comments are invited on second draft of document on the website.
- Discussion of database content and structure:
Suggestions for content of locus-specific databases:
- Follow nomenclature agreement.
- Give context for mutations.
- Record all allelic variation in coding sequence as they may have an effect on gene function. The definition of mutation vs. polymorphism was discussed as a problem. The term "Allelic variants" was thought to solve this problem.
- Structure discussed - flat file vs. relational database, sequence centered, etc.
- Essential to have formal documentation.
D. Central Database Working Group Report.
1. OMIM - Reported by Victor McKusick.
- Catalogs 1st disease producing mutation; ~1st dozen mutations when there are many mutations; mutations with distinct phenotype; mutations with distinct population distribution; mutations with particularly historic interest; unusual mutational mechanisms such as gene conversion; mutations in promotor, cap site, termination codon etc.; some DNA polymorphisms cataloged such as DNA methods for typing of blood groups or modifier of cis mutation.
OMIM links to single locus databases, Cardiff (HGMD). Since it has phenotypic variation it is being used by the public to obtain clinical information.
OMIM is moving toward multicenter, multiauthorship. It reviews about 20 journals and goes on line promptly.
2. GDB-Reported by Stan Letovsky
- GDB will shut down in July with no further annotation. This is due to the loss of funding from the Dept. of Energy. Human Gene Nomenclature function will be continued. GDB will probably maintain a read only, static mode.
3. HGMD (Cardiff) - Reported by David Cooper (written report & handout)
(See long report in Newsletter 3-: http://ariel.ucs.unimelb.edu.au:80/~cotton/news.htm)
4. EBI - Reported by Heikki Lehvaslaiho
- EBI gives a uniform view of locus-specific databases.
- Provides links to single-locus databases.
- Validation of core data begun - automated approach. HUMUT is a database with validation checks for discrepancies between cDNA and amino acid sequence.
- Need to have reference sequence in databases.
- Notes bias in curation of mutations against genomic deletions.
5. GENATLAS - Reported by Jean Frezal
- Phenotype orientated database.
- Should link to locus specific databases.
- Clinical disorders classified by organ, tissue or affect system.
- Different diseases due to mutations in the same gene are reported under separate headings; link is through the gene's symbol.
- In general, molecular defects are to cataloged, except for mutations in the mitochondrial genome.
6. Mutation View - Reported by Nobuyoshi Shimizu.
E. Copyright and Data Protection - Reported by Doug Wallace.
1. Security of LS databases and sustainability of databases
- Longevity - maintenance of data accrual. Physical and fiscal infrastructure is important.
- Protection against database degradation i.e.,. erroneous entry, sabotage, system failure. Need mirror copy that is not accessed by public.
- Protection from misappropriation of data, unauthorized transfer to second site (commercial organization) unauthorized distribution from second site.
2. Copyright and the web.
a. USA law
- Protects works of authorship. Can register in the US copyright office for life + 50 years. Employer owns "Work made for hire" for 75 years after publication. If data is transferred, permission is needed to use it; a license is needed even if there is no copyright notice on the material. Material on the web can be copyrighted, even home pages.
- Cases where a use license may not be required:
"Fair use" - small amounts of factual material may not require a license.
"Public domain" - not protected by copyright, copyright may have lapsed.
- "Ideas and facts" are not themselves protected and can be used.
b. European Union Data Protection Directive
Pro: Private sector database management groups.
- Goes into effect this year - Oct. 24, 1998.
- Provides new legal protection for databases. Different from copyright.
- Copyright protection is for original selection and arrangement of facts.
"Sui Generis" protection is for "one of a kind". It is statutory protection for non-original material, prohibiting the extraction of a substantial part of any database that reflected significant investment. This is not protected in the USA. Protection of data itself is 15years from availability, renewal with each update - gives infinite lifespan.
- Locus-specific databases could receive both protections.
- Alternative Views:
- Computer databases are new, a new way of handling information. Whole is greater than the sum of the parts. Current copyright law protects expression, not facts.
- Without protection, small projects will die. Since the European Union has protection, the rest of the world needs this. Clinton administration in favor of it.
Con: Anyone for free exchange of information
US constitution - protects expression, not facts. Any fact in any table can be copied at will. Protection of rights of individual curator vs. right of society for freedom of information.
If there is a document describing the database design, this can be copyrighted. Need to have a formal informatics document. If the initiative comes under HUGO, HUGO directory becomes a value-added document.
F. Quality control - Reported by Richard Cotton
Need for curators to check accuracy of data in databases for the following omissions:
- Lack of expression studies.
- Lack of "polymorphism" test. Is the variant present in screen of 100 alleles?
- Lack of segregation test. No family data available.
- Problems of interpretation of unusual effects.
- Information regarding proof a causation of disease by a mutation should be in database:
- Found in a second PCR product from the patient?
- Segregates with the disease?
- Conserved during evolution?
- Not present in 50 normals (100 alleles)?
This database will soon be launched.
- Acquisition of data on new SOD1 mutations. Complete record of genotype/phenotype correlations.
- Structure: database will consist of mutation entries, patient, family and depositor details,
- clinical details, neuropathology, SOD1 enzymatic activity, material availability, references.
- H. Plan next meeting in conjunction with 1998 ASHJ in Denver. Question of 1 or 2 days.
Turin Meeting-Reported by Arleen Auerbach.
Posted 29th May 1998, by Rania Horaitis