IMGT/HLA Database

Ambiguous Allele Combinations

The use of Sequence Based Typing (SBT) as a method for defining the HLA type is well documented, most SBT typing strategies currently employed use the exon 2 and exon 3 sequences for HLA class I analysis and exon 2 alone for HLA class II analysis. Due to the heterozygous nature of the SBT analysis the combinations of many pairs of alleles may give an ambiguous typing result. The document includes a list of all alleles which are identical over exons 2+3 for HLA class I and exon 2 for HLA class II, in addition all ambiguous results obtained when using the alleles included in this release are also included.

From 01-April-2010, all HLA alleles that have identical nucleotide sequences across the exons encoding the peptide binding domains (exon 2 and 3 for HLA class I and exon 2 only for HLA class II alleles) will be designated by an upper case ‘G’ which follows the allele designation of the lowest numbered allele in the group. A full list of the new G Groups can be seen at http://hla.alleles.org/nomenclature/g_groups.html.

Generating Ambiguous Allele Combinations

The algorithm used to generate the ambiguous combinations has recently been updated to better represent alleles which contain unsequenced regions. For the alleles in question, the sequence of an alternate allele has been used to extend the sequence over this region. The choice of alternate allele has been determined by sequence homology to the closest known full exon 2 (or 3) sequence and only used when there is a high probability that the sequence used would be shown to be correct if the region was fully sequenced. The list of alleles containing unsequenced regions and the alternate alleles used to infer the missing sequence are detailed in the file.

Several DRB1 alleles are not sequenced for the dimorphic nucleotide at position 357. It would therefore be inaccurate to assign a base to these sequences at this position. For this reason the sequences have been truncated to include only nucleotides 101 to 356, in the DRB1 analysis.

In the case of unsequenced regions that cannot be accurately be inferred from known sequences with a high level of confidence the allele has been omitted from the analysis.

We recognise that future sequencing of unsequenced regions may reveal disparity between the predicted sequence and the newly sequenced region. We therefore welcome any further information which will help improve analysis of these regions.

Download Files

The IMGT/HLA Ambiguous Allele Combinations file is available as both a PDF file and Microsoft Excel file.

Example Output

he following text is an example only, the full list for HLA-A can be found in the PDF file. Once the PDF file has been downloaded it can be searched like any other text document. In order to perform a search in a PDF file follow these steps.

• Open the ambiguities file in Acrobat Reader
• Under the "Edit" menu select the "Find" option
• You can now enter an allele name into this box and search the text contained in the PDF file.

There are a number of more advanced options available under the "Search" facility.

Sequences identical over exons 2 + 3

Ambiguous typing combinations over exons 2+ 3

Continued ...

Information

For more information about the database, IMGT/HLA queries (including website) or to subscribe to the IMGT/HLA mailing list please contact IMGT/HLA Support.