P067 How different is gamma block in HLA matched (10/10) unrelated pairs detected by next generation sequencing (NGS)?

Aim At least four genomic blocks have been identified in the MHC. Gamma block includes the polymorphic Complement genes and is located between the genomic blocks that include the HLA-C/B and HLA-DRB/DQB genes. Matching for SNPs in the Gamma block has been shown to be important for donor selection in Hematopoietic Stem Cell Transplant (HSCT) to assist in the distinguishing HLA haplotype matched/HLA genotype matched donors from HLA haplotype mismatched/HLA genotype matched donors. Methods We have used a NGS method to sequence 4 PCR products spanning 12.4 kb of the C4 genes. The cohort comprised of 988 samples from HSCT patients transplanted at City of Hope (2006–2012) and their corresponding 10/10 HLA matched donors. HLA-DPB1 results are available on all pairs. The initial validation of the method was performed using family members for HLA matched siblings ( n  = 13). Results Only 40% of pairs were identical comparing 25 previously described SNP and one Indel, known to be linked to HLA haplotypes. Positions: 9881, 14563, 14831, 19588 and 20170 differ in more than 80 pairs (see Picture). Total of 300 polymorphic positions were characterized, and 73/300 were observed in more than 10 individuals, without correcting for copy-number variation. The statistical analysis to test the importance of matching polymorphisms in transplant outcomes is still in progress. Conclusion The high diversity observed within the C4 genes of the gamma block indicate that they can be used as informative markers for donor selection. Download high-res image (182KB) Download full-size image H. Hogan: Stock Shareholder; Company/Organization; Illumina. C. Wirtz: Stock Shareholder; Company/Organization; Illumina. D. Sayer: Stock Shareholder; Company/Organization; Illumina.