P001 On the occurrence of non-cwd alleles in the german dkms donor database

Abstract

The list of Common and Well-Documented (CWD) alleles comprises alleles that have been either observed at pertinent exons at least 5 times via DNA typing technologies (SBT, NGS) in unrelated individuals (well-documented) or have a frequency higher than 0.001 in populations of at least 1500 individuals (common). We compared the current CWD list 2.0.0 to the DKMS Germany database of more than 4.5 M unrelated stem cell donors. Using results with allelic resolution for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1, we determined the number of occurrences for each allele. As the CWD list is based on IMGT/HLA release 3.9.0 (July 2012), we first analyzed typing results prior to this date. We then included typing results into the analysis up to April 2016. As a rule, whenever a two-field allele in the CWD list was represented in our database by three or four field allele designations, we treated it as CWD. Whenever a two- or three-field allele in the database had a longer equivalent, it was treated alike. Based on alleles known in HLA release 3.9.0, we found 396 (991) individual alleles typed prior to 2012 (April 2016) that were observed more than 5 times in our database, but not listed as CWD. Of the 396 (991) non-CWD alleles, 18 (60) alleles are part of a G-code in the CWD list. Including alleles introduced after HLA release 3.9.0 in our analysis, additional 134 alleles met the CWD requirement. By using the CWD list, for example, the multi-allele code HLA-A*25:AC might be reported as A*25:01 and A*25:03 (non-CWD) only in a footnote although it was observed 97 (176) times in our analysis. Some registries also accept results from CT as high resolution ignoring ambiguous pairs where at least one partner is non-CWD. Our results suggest that the application of the CWD list in laboratories to omit ambiguous results or to not include non-CWD alleles when transmitting CT results should be avoided. Given the increasing availability of high-resolution NGS-based phased typing results, the CWD list should be updated in an automated fashion from data available on BMDW. Download : Download high-res image (249KB) Download : Download full-size image