Nomenclature for factors of the HLA system, 2004

Abstract

Following the decision to hold their next full meeting after the 14th International Histocompatibility Workshop in 2005, the WHO Nomenclature Committee for Factors of the HLA System has decided to publish an interim report listing updated tables of alleles including those assigned since the publication of the last full report in 2002 (1). The alleles named during the period follow the principles established in previous reports (1–17). As emphasized in previous reports, there are required conditions for acceptance of new sequences for official names. Where a sequence is obtained from cDNA, or where PCR products are subcloned prior to sequencing, several clones should have been sequenced. Sequencing should always be performed in both directions. If direct sequencing of PCR amplified material is performed, products from at least two separate PCR reactions should have been sequenced. In individuals who are heterozygous for a locus, and where one of the alleles is novel, the novel allele must be sequenced in isolation from the second allele. Thus an allele sequence which is derived using a sequence based typing (SBT) methodology, where both alleles of a heterozygous individual are sequenced together, is insufficient evidence for assignment of an official designation. Sequence derived solely from the primers used to amplify an allele should not be included in the submitted sequence. Where possible, a novel sequence should be confirmed by typing of genomic DNA using a method such as PCR-SSOP or PCR-SSP. Where a new sequence contains either a novel mutation or a previously unseen combination of nucleotides (sequence motif), this must be confirmed by a DNA typing technique. This may require the use of newly designed probes or primers to cover the new mutation; these reagents should also be described. An accession number in a databank should have been obtained. Sequences may be submitted to the databases online at the following addresses: EMBL: http://www.ebi.ac.uk/Submissions/index.html GenBank: http://www.ncbi.nlm.nih.gov/GenBank/index.html DDBJ: http://www.ddbj.nig.ac.jp/sube.html Full-length sequences are preferable though not essential; the minimum requirements are complete exons 2 and 3 for an HLA class I sequence and complete exon 2 for an HLA class II sequence. Where a novel sequence differs only within an intron or other non-coding part of the gene, a full length sequence must be obtained, which covers all coding and non-coding regions. In the absence of a full length genomic sequence from the most closely related allele, it may be required that this also be sequenced and submitted before a name can be assigned to the novel sequence. Where possible, a paper in which the new sequence is described should be submitted for publication. DNA or other material, preferably cell lines, should, wherever possible, be made available in a publicly accessible repository or alternatively, at least in the originating laboratory. Documentation on this will be maintained by the WHO Nomenclature Committee. Submission of a sequence to the WHO Nomenclature Committee should be performed using the online submission tool available at http://www.ebi.ac.uk/imgt/hla/subs/submit.html. Researchers are expected to complete a questionnaire relating to the sequence and provide a comparison of their new sequence with known related alleles. If the sequence cannot be submitted using the online web tools, researchers should contact [email protected] directly for details of alternative submission methods. Although at present it is only a recommendation that full-length sequences of the coding region of novel alleles be submitted it was widely felt that in the future this should become a requirement for submission. Such requirement would remove many of the currently encountered ambiguities in the assignment of names to alleles for which partial sequences have been submitted and should not be burdensome as sequencing techniques have improved substantially since the submission conditions were first devised. In cases where novel mutations or polymorphisms are detected in non-coding regions of the gene, it will be a requirement that full-length sequences be submitted of both the novel allele and its most closely related allele. It should be noted with some caution that cells from which only partial sequences have been obtained may later be shown to have different or novel alleles when further sequencing is performed. This is of particular importance in cases where partial sequences of what appears to be the same allele have been obtained from several different cells. In such cases, all cells studied have been listed in this report. Current practice is that official designations will be promptly assigned to newly described alleles in periods between Nomenclature Committee meetings, provided that the submitted data and its accompanying description meet the criteria outlined above. A list of the newly reported alleles is published each month in nomencl