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  • Title: HLA-C polymorphisms and PCR dropout in exons 2 and 3 of the Cw*0706 allele in sequence-based typing for unrelated Chinese marrow donors.
    Author: Deng Z, Wang D, Xu Y, Gao S, Zhou H, Yu Q, Yang B.
    Journal: Hum Immunol; 2010 Jun; 71(6):577-81. PubMed ID: 20226825.
    Abstract:
    To evaluate the accuracy of SBT protocols for HLA-C and to better understand the HLA-C polymorphism in Chinese, 1795 unrelated CMDP donors were typed at exons 2, 3, and 4 of the HLA-C gene using the Atria commercial kit. Of the study subjects, 1768 showed conclusive typing results, whereas the other 27 showed inconclusive results. Subsequent full-length cloning and haplotype sequencing showed that 11 of the 27 inconclusive results could be explained by the presence of nine novel alleles identified: Cw*0130, 0624, 070206, 075602, 0766, 0767, 0820, 0821, and 0827. These novel alleles were generated by a total of 10 coding-region substitutions, eight of them being located in the antigen-binding groove. Cw*0766 and Cw*075602 were detected three and two times, respectively, in the 1795 donors. The other 16 inconclusive samples were retested by SBT using our in-house PCR primers; all of them were found to carry Cw*0706, which dropped out in exons 2 and 3 in the initial PCR using the commercial primers amplifying from 5' UTR to intron 3. Our results showed the importance of the full-length genomic sequence and intronic SNPs for the development of more accurate SBT. The allele distribution and novel alleles detected in this study also provide further insights into the HLA-C polymorphism in the Chinese Han population.
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