Condition of acceptence for new alleles

The IPD-IMGT/HLA Database has a set of minimum requirements for sequence and metadata. Please review these requirements carefully before making a submisison to the database.

Requirements checklist

  1. Where a sequence is obtained from cDNA, or where PCR products are subcloned prior to sequencing, several clones should have been sequenced.
  2. Sanger sequencing should always be performed in both directions.
  3. If direct sequencing of PCR amplified material is performed, products from at least two separate PCR reactions should have been sequenced.
  4. When using next-generation or third generation sequencing, the unequivocal phasing of all polymorphisms should be confirmed across the complete sequence.
  5. 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 that is derived using a Sanger Sequencing-Based Typing (SBT) methodology, where both alleles of a heterozygous individual are sequenced together, is insufficient evidence for assignment of an official designation.
  6. Sequence derived solely from the primers used to amplify an allele should not be included in the submitted sequence.
  7. A novel sequence should be confirmed by repeat sequencing or employing a secondary DNA based typing technique to confirm the sequence.
  8. An accession number in a databank should have been obtained. Sequences may be submitted to the databases online at the following addresses:
    • ENA: https://www.ebi.ac.uk/submission/index.html
    • GenBank: https://www.ncbi.nlm.nih.gov/WebSub/
    • DDBJ: https://www.ddbj.nig.ac.jp/submission-navigation-e.html
  9. Full-length sequences are preferable, though not essential; the current minimum requirements are complete exons 2 and 3 for an HLA class I sequence and complete exon 2 for an HLA class II sequence. It is anticipated that we will move to requiring full-length sequences in the near future and every effort should be made to submit full-length sequences, as sequencing technology has improved substantially and makes this very achievable.
  10. Where a novel sequence differs only within an intron or other non-coding part of the gene, a full-length sequence must be obtained that 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.
  11. Sequences should be submitted for naming prior to publication and details of the official names assigned included in the manuscripts published subsequently.
  12. Sequences derived solely from tumour material will not be considered for assignment of official allele nomenclature.
  13. Sequences derived from patients with malignant haematological disease should confirmed to be in the germline of the patient, using DNA derived from non-haematopoietic tissue, or in first degree relatives with the same allele.
  14. The complete HLA phenotype for the HLA-A, -B, -C and -DRB1 genes, with at least two-field resolution, should be submitted for the material in which a novel allele has been defined.
    In addition, the sample should have been characterised for the second allele at the locus of interest in a heterozygous individual, to the same level of resolution as that obtained for the novel allele.
  15. 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.
  16. Submission of a sequence to the WHO Nomenclature Committee should be performed using the online submission tool available at:

    www.ebi.ac.uk/ipd/imgt/hla/submission/

    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 ipdsubs@anthonynolan.org 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 quarter in nomenclature updates in the journals HLA, Human Immunology and the International Journal of Immunogenetics. The listing of references to new sequences does not imply priority of publication. The use of numbers or names for alleles, genes or specificities which pre-empt assignment of official designations by the Nomenclature Committee is strongly discouraged.