Novel HLA Allele Identified

In May, 2020, we reported on the likely discovery of a novel HLA-B allele (https://bit.ly/3TsmmtY). At that time, we performed HLA typing and sequence alignments against the then current version of the IMGT/HLA database, namely, v.3.38.0. The sample was typed as B*27:05:02:01/B*39:06:02:01 with a single exon mismatch.

Fig. 1. Initial HLA typing.

Our client requested that we rerun and retype their sample against the now current version of the IMGT/HLA database, namely, v.3.49.0. It turns out that it now types as B*27:259/B*39:06:02:0 with no exon mismatches.

Fig. 2. Reanalysis of initial sample.

From May, 2020, to September, 2022, the database has undergone 11 updates (https://bit.ly/3eaJZqX).  And the number of submitted alleles increased by 9,119 (https://bit.ly/3cz4zAR).  If we dig deeper, we find that allele B*27:259 was assigned on May 31, 2022, and would have first appeared in the v.3.39.0 version of the database (https://bit.ly/3QdlV3H). From this we infer that we probably did find a novel allele back in 2020 but it was then added to the database in 2022 by others who presumably found the same allele.

The lesson learned here is that you should permanently archive the sequencing raw data files (FASTQ) so they can be reanalyzed in the future with newer versions of the HLA database and newer versions of the HLA typing algorithms.  We always encourage our clients to do this.