44-OR

Abstract

Most HLA alleles described in the IMGT/HLA database are very rare. The Common and Well Documented (CWD) allele list was created in 2007 to identify the subset of HLA alleles likely to be observed again, and the CWD list was revised in 2013 (CWD2). Our aim was to identify which protein-level CWD2 alleles were estimated from US registry HLA data. We evaluated allele frequency coverage of CWD2 “Common” and “Well Documented” categories in estimated haplotype frequencies for A,C,B,DRB1,DQB1 loci derived from all DNA-based registry typings in 26 US populations (http://bioinformatics.nmdp.org/FullRegistryHaplo/). We also identified CWD2 alleles not present in the US frequencies, the most frequent non-CWD2 alleles, and percentage of single-pass SBT requiring additional typing to meet CWD2-based typing resolution requirements. Common CWD2 alleles constituted a minimum of 91.1% of allele frequency at any locus in any population. Inclusion of Well Documented CWD2 alleles reached 99.5% coverage. 5 CWD2 alleles, all Well Documented category, were not observed in US frequencies (B*40:22N, B*52:21 C*07:67, DRB1*04:12, DRB1*14:14), however all 5 were estimated in a preliminary 2012 global BMDW dataset. Additionally, there were haplotype frequency estimates for many non-CWD2 alleles (514 A, 257 C, 707 B, 276 DRB1, 49 DQB1). The estimated percent of single-pass SBT typings with CWD2 genotypic ambiguity was at most 16.6% at any locus in any population, up from 9.6% for CWD1. Available US haplotype frequencies offer near complete coverage of CWD2 alleles, and offer additional advantages of providing population-specific allele frequency and haplotype linkage information. Publication of global BMDW haplotype frequencies is a goal of an international collaborative effort by the World Marrow Donor Association (WMDA) Registry Diversity working group, and will cover all CWD2 alleles when complete. The most frequenct non-CWD alleles may predict future additions to the living CWD list.