116-P: A DRB103/DRB108 ALLELE RECOMBINATION WITHIN EXON 2

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Aim

Hema-Quebec enrolls around 2000 new potential stem cell donors in its registry every year with the goal of increasing its proportion for ethnic diversity. In 2011, the ethnic and mixed (multiple ethnicity) donors of the Hema-Quebec registry represented less than 8% of the registry, although the ethnicity of the population in urban centers reached more than 16%. An effort is made to increase not only the non Caucasian contribution, but also some of the European groups which can arbor particular alleles and haplotypes. We report here the identification of a gene recombination within Exon 2 of the DRB1 allele in a donor with Slavic origin.

Methods

The HLA-A, -B, -C and -DRB1 were first analysed by SSO in low resolution and then sequenced by using PCR reactions of exons 2, 3 and 4 for locus C, exons 2 and 3 for A, B and DQB1, exon 2 for DRB1. The new DRB1 allele couldn’t be typed by SSO Luminex and could neither be confirmed by SSP since no reactivity pattern was available for this new allele.

Results

The HLA-DRB1 SBT analysis of the donor sample demonstrated a modified sequence with a series of substitutions at the beginning of exon 2 of the DRB103:01. These modifications were identified as being the first part of the DRB108 exon 2. The donor’s family members were also analysed to trace back the origin of this recombination. The recombinant DRB1 allele was confirmed by another ASHI laboratory. When analyzed by SSO and SSP, the mutation could not be seen and no final typing could be obtained.

Conclusions

Isolated mutations occur frequently as well as crossing over between loci, mainly A and C. In contrast, recombination within an exon is a rare and exciting event. This example is a good one which plays in favor of the orientation taken by Hema-Quebec to increase the HLA diversity of the stem cell donor registry, not only by increasing the ethnic diversity of the donor pool, but also by targeting populations and groups of different origins susceptible to have particular haplotypes and alleles.

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