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Draft 3; 29Nov96
RECOMMENDATIONS FOR A NOMENCLATURE SYSTEM FOR HUMAN GENE MUTATIONS
Prepared by Stylianos E Antonarakis
This document is created as a result of the meeting on "locus-specific mutation databases" held on March 24, 1996 in Heidelberg, Germany and
the "Mutation Database" meeting on October 29, 1996 in San Francisco,
California. As a chairperson of the Nomenclature committee, I had
accepted the task preparing and circulating a document with
recommendations for debate, further discussions and most importantly for
final approval / acceptance at the October 1996 meeting in San
Francisco. The first draft of this document (5 Aug 96) was distributed to a number of investigators, the majority of which are co-authors in
the Beaudet et al and Beutler et al papers (see below). This second
draft (5 Sep 96) contained modifications according to their suggestions,
opinions and criticisms. Furthermore, many colleagues had offered
suggestions, criticisms, and ideas through electronic communication.
During the October 29, 1996 meeting in San Francisco, there was a
sufficient discussion of these recommendations and it was agreed that
another, further modified draft of the document would be posted on the
"World Wide Web" for final debate for a period of 6 weeks. Then, this
set of initial recommendations would be published as guidelines for
Two manuscripts were recently published in the journal "Human Mutation" that contain mutation nomenclature recommendations: "Update on nomenclature for human gene mutations" by Beaudet et al., Hum.Mut. 8: 197-202, 1996 and "Mutation nomenclature: nicknames, systematic names and unique identifiers" by Beutler et al., Hum.Mut. 8: 203-206, 1996. These documents present the views of the authors after discussions during the October 19, 1994, Montreal and the October 24-25, 1995 Minneapolis meetings. Other published papers/letters on nomenclature issues include the following: Beaudet & Tsui, Hum.Mut. 2: 245, 1993; Beutler, Am.J.Hum.Genet. 53: 783, 1993; Antonarakis & McKusick, Hum.Mut. 4: 166, 1994.
It is obvious that the most unambiguous nomenclature system is that based on genomic DNA. Even in that case, however, length polymorphisms create a problem in the numbering of nucleotides and therefore a standard, reference sequence ought to be established, preferably by the experts. Unfortunately, the entire genomic sequence is only known for a minority of human genes. For the vast majority of genes, the known sequence is that of cDNA. The existence of more than one transcription start site, alternative splicing and utilization of alternative exons and variable number of repeats complicate the nucleotide numbering and here too a reference sequence needs to be established. The nomenclature, at least in the present state of the human genome development, needs to be accurate, unambiguous, but flexible. The nucleotide change must always be included in the original report; however other names, for example based on amino acid changes, may be used. The genomic DNA-based nomenclature was termed "systematic" by Beutler at al, while all other mutation names were considered as "trivial" or "common" by these authors.
A list of recommendations follows:
No recommendations are made at this time for more complex mutations.
Detailed description for such mutations and nomenclature proposals can
be usually found in the original reference or by the unique identifier.
A second phase of recommendations will deal with such issues in the
future. In addition, the consequence of a mutation (frameshift,
particular splicing abnormality, exon skipping etc) is not included in
the mutation name. However, investigators that maintain mutation
databases are encouraged to include a field of mutation consequence or
mutation mechanism (if known) in their databases.
This version of this document will be posted for 6 weeks starting 2nd December, 1996.
After this date the recommendations will be published as guidelines for investigators.
Please forward to my email address (email@example.com) your comments, suggestions, criticisms.
We would also invite you to co-sign this document (if you do not have major disagreements with its content). Your participation and names will appear in the published version of these recommendations. Please include your institution, address, and email coordinates.
Stylianos E. Antonarakis MD, DSc
Professor of Medical Genetics
University of Geneva Medical School
9 avenue de Champel