The probability of HLA-C matching between patient and unrelated donor at the molecular level: Estimations based on the linkage disequilibrium between DNA typed HLA-B and HLA-C alleles Journal Article
| Authors: | Prasad, V. K.; Heller, G.; Kernan, N. A.; O'Reilly, R. J.; Yang, S. Y. |
| Article Title: | The probability of HLA-C matching between patient and unrelated donor at the molecular level: Estimations based on the linkage disequilibrium between DNA typed HLA-B and HLA-C alleles |
| Abstract: | Background. Recent evidence suggests a more significant role of HLA-C as a target of alloreactions after bone marrow transplantation than previously suspected. Although linkage disequilibrium (LD) between HLA-B -and -C serogroups is well documented, the level of LD at the allelic level is not known. In this study, we determine the LD between HLA-B and -C alleles and estimate the probability of molecular HLA-C matching between unrelated individuals who match for both HLA-B alleles. Methods. The study included 727 haplotypes from 849 individuals who were HLA-A, -B, -C and -DRB1 typed by high-resolution PCR-SSOP technique. Zelterman's statistic was used to test for global LD between HLA loci. LD between specific HLA-B and -C allelic combinations was calculated from their observed and expected frequencies in the study haplotypes. The probability of HLA-C matching for specific HLA-B allele was estimated from contingency table generated from the HLA-B and -C haplotypes. Results. HLA-C was found to exist in LD with HLA-A and -B, as well as -DRB1, loci; however, it was strongest between HLA-B and -C loci. A marked variability in the level of LD between specific HLA-B and -C alleles was noticed. A strong LD was seen in some allele pairs like B*0702-Cw*0702, B*3501-Cw*0401, and B*0801-Cw*0701. The overall estimated probability of HLA-C matching between unrelated individuals that match for both HLA-B alleles is 42.25%. For 237 (72.99%) of 325 combinations involving the 25 commonest HLA-B alleles, the estimated probability that the HLA-B-matched unrelated individuals will match for both HLA-C alleles is less than 50%. In addition, a 100% probability of matching for both HLA-C alleles is expected only if both individuals bear either B*0801/B*0801 or B*4901/B*4901 or B*0801/B*4901. Probability tables for common alleles are presented. Conclusions. We conclude that, despite matching for both HLA-B alleles by high resolution DNA typing and the presence of a strong LD between HLA-B and HLA-C loci, unrelated individuals are more likely to mismatch rather than match for one or both HLA-C alleles. |
| Keywords: | polymerase chain reaction; allele; gene locus; genetic variability; alleles; gene frequency; haplotypes; linkage disequilibrium; haplotype; hla matching; tissue donors; dna; probability; hla-c antigens; bone marrow transplantation; hla-b antigens; hla system; organ donor; histocompatibility testing; gene linkage disequilibrium; humans; human; priority journal; article |
| Journal Title: | Transplantation |
| Volume: | 68 |
| Issue: | 7 |
| ISSN: | 0041-1337 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 1999-10-15 |
| Start Page: | 1044 |
| End Page: | 1050 |
| Language: | English |
| DOI: | 10.1097/00007890-199910150-00024 |
| PUBMED: | 10532548 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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