Contents -

New Alleles

With the increased use of high resolution typing techniques like SBT in the diagnostic centers, the discovery of new HLA alleles has gained momentum. In October 2006, the IMGT/HLA version 2.15 database contained 2607 alleles whereas in the same month of 2007 the IMGT/HLA database 2.19 contained 3043 alleles. This is an increase of 436 alleles in 365 days! So on average a new HLA allele is discovered each day. This demonstrates that tissue typers using high resolution techniques should be aware of new alleles whenever they type samples.

In SBTengine there are several levels of the analysis process where a new allele can be encountered.

Level 1
When a new sample is loaded in the Sequence Overview for analysis a list of inconsistencies is generated. Whenever you find an inconsistency that does not match the IMGT/HLA database and you are convinced of the correct basecalling based on the electropherogram(s), you may have discovered a new allele. Do not neglect the electropherogram information and change the basecalling in whatever the IMGT/HLA database shows. Such an action may result in incorrect allele assignment and thus a wrong typing result.
The analysis process can not be continued in an ordinary fashion when this situation occurs because the inconsistency remains. You may resolve this by taking a note of the position of the inconsistency, where no match with the IMGT/HLA database is possible. Subsequently, you change the basecalling at this position in an "N", continue to resolve the remaning inconsistencies and follow the regular analysis process until an allele assignment is found. Be aware that the allele assignment shown is not the final allele assignment, but a near match with a variation at the position of the inconsistent position you took a note of. This new allele needs to be reported to the IMGT/HLA database. You can find more information on the requirements for submission on the IMGT/HLA website. Alternatively, you may contact us at info@gendx.com to assist you with the validation and submission of the new allele.

Level 2
The second level where a new allele can be encountered in SBTengine is in the procedure of checking the crucial positions. In this case you might not have an allele assignment when the crucial positions list is displayed and even when you've checked them all. In this case you can see the near match at the top of the crucial positions list with a basecalling suggestion. The new allele resembles the near match with exception of the different basecall of this first near match. Again, this new allele needs to be reported to the IMGT/HLA database. You can find more information on the requirements for submission on the IMGT/HLA website. Alternatively, you may contact us at info@gendx.com to assist you with the validation and submission of the new allele.